References
- De Duve C, Wattiaux R. Functions of lysosomes. Annu Rev Physiol. 1966;28(1):435–492.
- Klionsky DJ. Autophagy revisited: a conversation with Christian de Duve. Autophagy. 2008;4(6):740–743.
- Fimia GM, Stoykova A, Romagnoli A, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447(7148):1121–1125. DOI:https://doi.org/10.1038/nature05925.
- Gan B, Peng X, Nagy T, et al. Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways. J Cell Biol. 2006;175(1):121–133. DOI:https://doi.org/10.1083/jcb.200604129.
- Kuma A, Hatano M, Matsui M, et al. The role of autophagy during the early neonatal starvation period. Nature. 2004;432(7020):1032–1036. DOI:https://doi.org/10.1038/nature03029.
- Qu X, Yu J, Bhagat G, et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J Clin Invest. 2003;112(12):1809–1820. DOI:https://doi.org/10.1172/JCI20039.
- Saitoh T, Fujita N, Jang MH, et al. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008;456(7219):264–268. DOI:https://doi.org/10.1038/nature07383.
- Tsukamoto S, Kuma A, Murakami M, et al. Autophagy is essential for preimplantation development of mouse embryos. Science. 2008;321(5885):117–120. DOI:https://doi.org/10.1126/science.1154822.
- Yue Z, Jin S, Yang C, et al. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci U S A. 2003;100(25):15077–15082. DOI:https://doi.org/10.1073/pnas.2436255100.
- Hughes T, Rusten TE. Origin and evolution of self-consumption: autophagy. Adv Exp Med Biol. 2007;607:111–118.
- Moruno-Manchon JF, Uzor NE, Ambati CR, et al. Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes. Cell Death Dis. 2018;9(5):521. DOI:https://doi.org/10.1038/s41419-018-0599-5.
- Valera E, Spencer B, Mott J, et al. MicroRNA-101 modulates autophagy and oligodendroglial alpha-synuclein accumulation in multiple system atrophy. Front Mol Neurosci. 2017;10:329.
- Vaccari I, Carbone A, Previtali SC, et al. Loss of Fig4 in both Schwann cells and motor neurons contributes to CMT4J neuropathy. Hum Mol Genet. 2015;24(2):383–396. DOI:https://doi.org/10.1093/hmg/ddu451.
- Bremer J, O’Connor T, Tiberi C, et al. Ablation of Dicer from murine Schwann cells increases their proliferation while blocking myelination. PLoS One. 2010;5(8):e12450. DOI:https://doi.org/10.1371/journal.pone.0012450.
- Shi G, Shi J, Liu K, et al. Increased miR-195 aggravates neuropathic pain by inhibiting autophagy following peripheral nerve injury. Glia. 2013;61(4):504–512. DOI:https://doi.org/10.1002/glia.22451.
- Jamart C, Naslain D, Gilson H, et al. Higher activation of autophagy in skeletal muscle of mice during endurance exercise in the fasted state. Am J Physiol Endocrinol Metab. 2013;305(8):E964–74. DOI:https://doi.org/10.1152/ajpendo.00270.2013.
- Laporte J, Hu LJ, Kretz C, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996;13(2):175–182. DOI:https://doi.org/10.1038/ng0696-175.
- Pagano AF, Py G, Bernardi H, et al. Autophagy and protein turnover signaling in slow-twitch muscle during exercise. Med Sci Sports Exerc. 2014;46(7):1314–1325. DOI:https://doi.org/10.1249/MSS.0000000000000237.
- Spaulding HR, Ludwig AK, Hollinger K, et al. PGC-1alpha overexpression increases transcription factor EB nuclear localization and lysosome abundance in dystrophin-deficient skeletal muscle. Physiol Rep. 2020;8(4):e14383. DOI:https://doi.org/10.14814/phy2.14383.
- Vergne I, Roberts E, Elmaoued RA, et al. Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy. Embo J. 2009;28(15):2244–2258. DOI:https://doi.org/10.1038/emboj.2009.159.
- Wang H, Dai J, Hou S, et al. Treatment of hepatocellular carcinoma with adenoviral vector-mediated Flt3 ligand gene therapy. Cancer Gene Ther. 2005;12(9):769–777. DOI:https://doi.org/10.1038/sj.cgt.7700843.
- Ashrafi G, Schlehe JS, LaVoie MJ, et al. Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol. 2014;206(5):655–670. DOI:https://doi.org/10.1083/jcb.201401070.
- Fu MM, Holzbaur EL. MAPK8IP1/JIP1 regulates the trafficking of autophagosomes in neurons. Autophagy. 2014;10(11):2079–2081.
- Rub C, Wilkening A, Voos W. Mitochondrial quality control by the Pink1/Parkin system. Cell Tissue Res. 2017;367(1):111–123.
- Stavoe AK, Hill SE, Hall DH, et al. KIF1A/UNC-104 transports ATG-9 to regulate neurodevelopment and autophagy at synapses. Dev Cell. 2016;38(2):171–185. DOI:https://doi.org/10.1016/j.devcel.2016.06.012.
- Wong YC, Holzbaur EL. The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. J Neurosci. 2014;34(4):1293–1305.
- Hirano A. Neuropathology of ALS: an overview. Neurology. 1996;47(4 Suppl 2):S63–6.
- Laferriere F, Polymenidou M. Advances and challenges in understanding the multifaceted pathogenesis of amyotrophic lateral sclerosis. Swiss Med Wkly. 2015;145:w14054.
- Peters OM, Ghasemi M, Brown RH Jr. Emerging mechanisms of molecular pathology in ALS. J Clin Invest. 2015;125(5):1767–1779.
- Shefner JM, Al-Chalabi A, Baker MR, et al. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol. 2020;131(8):1975–1978. DOI:https://doi.org/10.1016/j.clinph.2020.04.005.
- Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal. 2014;20(3):460–473.
- Chen Y, Klionsky DJ. The regulation of autophagy - unanswered questions. J Cell Sci. 2011;124(2):161–170.
- Ganley IG, Lam Du H, Wang J, et al. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009;284(18):12297–12305. DOI:https://doi.org/10.1074/jbc.M900573200.
- Itakura E, Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy. 2010;6(6):764–776.
- Yang Z, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol. 2009;335:1–32.
- Jung CH, Jun CB, Ro SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20(7):1992–2003. DOI:https://doi.org/10.1091/mbc.e08-12-1249.
- Hosokawa N, Hara T, Kaizuka T, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell. 2009;20(7):1981–1991. DOI:https://doi.org/10.1091/mbc.e08-12-1248.
- Burman C, Ktistakis NT. Regulation of autophagy by phosphatidylinositol 3-phosphate. FEBS Lett. 2010;584(7):1302–1312.
- Itakura E, Kishi C, Inoue K, et al. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19(12):5360–5372. DOI:https://doi.org/10.1091/mbc.e08-01-0080.
- Geng J, Klionsky DJ. The Atg8 and Atg12 ubiquitin-like conjugation systems in macroautophagy. ‘Protein modifications: beyond the usual suspects’ review series. EMBO Rep. 2008;9(9):859–864.
- Weidberg H, Shvets E, Elazar Z. Biogenesis and cargo selectivity of autophagosomes. Annu Rev Biochem. 2011;80(1):125–156.
- Yorimitsu T, Klionsky DJ. Autophagy: molecular machinery for self-eating. Cell Death Differ. 2005;12(Suppl 2):1542–1552.
- Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147(4):728–741.
- Lamb CA, Yoshimori T, Tooze SA. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14(12):759–774.
- Liang C, Lee JS, Inn KS, et al. Beclin1-binding UVRAG targets the class C Vps complex to coordinate autophagosome maturation and endocytic trafficking. Nat Cell Biol. 2008;10(7):776–787. DOI:https://doi.org/10.1038/ncb1740.
- Wurmser AE, Sato TK, Emr SD. New component of the vacuolar class C-Vps complex couples nucleotide exchange on the Ypt7 GTPase to SNARE-dependent docking and fusion. J Cell Biol. 2000;151(3):551–562.
- Sardiello M, Palmieri M, Di Ronza A, et al. A gene network regulating lysosomal biogenesis and function. Science. 2009;325(5939):473–477.
- Settembre C, Di Malta C, Polito VA, et al. TFEB links autophagy to lysosomal biogenesis. Science. 2011;332(6036):1429–1433. DOI:https://doi.org/10.1126/science.1204592.
- Lapierre LR, Kumsta C, Sandri M, et al. Transcriptional and epigenetic regulation of autophagy in aging. Autophagy. 2015;11(6):867–880. DOI:https://doi.org/10.1080/15548627.2015.1034410.
- Medina DL, Ballabio A. Lysosomal calcium regulates autophagy. Autophagy. 2015;11(6):970–971.
- Napolitano G, Ballabio A. TFEB at a glance. J Cell Sci. 2016;129(13):2475–2481.
- Puertollano R, Ferguson SM, Brugarolas J, et al. The complex relationship between TFEB transcription factor phosphorylation and subcellular localization. Embo J. 2018;37(11):11. DOI:https://doi.org/10.15252/embj.201798804.
- Cuervo AM, Wong E. Chaperone-mediated autophagy: roles in disease and aging. Cell Res. 2014;24(1):92–104.
- Tasset I, Cuervo AM. Role of chaperone-mediated autophagy in metabolism. FEBS J. 2016;283(13):2403–2413.
- Li WW, Li J, Bao JK. Microautophagy: lesser-known self-eating. Cell Mol Life Sci. 2012;69(7):1125–1136.
- Kondapalli C, Kazlauskaite A, Zhang N, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012;2(5):120080. DOI:https://doi.org/10.1098/rsob.120080.
- Dengjel J, Abeliovich H. Roles of mitophagy in cellular physiology and development. Cell Tissue Res. 2017;367(1):95–109.
- Heo JM, Ordureau A, Paulo JA, et al. The PINK1-PARKIN mitochondrial ubiquitylation pathway drives a program of OPTN/NDP52 recruitment and TBK1 activation to promote mitophagy. Mol Cell. 2015;60(1):7–20. DOI:https://doi.org/10.1016/j.molcel.2015.08.016.
- Matsumoto G, Shimogori T, Hattori N, et al. TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation. Hum Mol Genet. 2015;24(15):4429–4442. DOI:https://doi.org/10.1093/hmg/ddv179.
- Davis CH, Kim KY, Bushong EA, et al. Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci U S A. 2014;111(26):9633–9638. DOI:https://doi.org/10.1073/pnas.1404651111.
- Decker CJ, Parker R. P-bodies and stress granules: possible roles in the control of translation and mRNA degradation. Cold Spring Harb Perspect Biol. 2012;4(9):a012286.
- Erickson SL, Lykke-Andersen J. Cytoplasmic mRNP granules at a glance. J Cell Sci. 2011;124(3):293–297.
- Buchan JR, Kolaitis RM, Taylor JP, et al. Eukaryotic stress granules are cleared by autophagy and Cdc48/VCP function. Cell. 2013;153(7):1461–1474. DOI:https://doi.org/10.1016/j.cell.2013.05.037.
- Meyer H, Bug M, Bremer S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol. 2012;14(2):117–123.
- Mijaljica D, Prescott M, Devenish RJV. ATPase engagement in autophagic processes. Autophagy. 2011;7(6):666–668.
- Ossareh-Nazari B, Bonizec M, Cohen M, et al. Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy. EMBO Rep. 2010;11(7):548–554. DOI:https://doi.org/10.1038/embor.2010.74.
- Kaushik S, Massey AC, Mizushima N, et al. Constitutive activation of chaperone-mediated autophagy in cells with impaired macroautophagy. Mol Biol Cell. 2008;19(5):2179–2192. DOI:https://doi.org/10.1091/mbc.e07-11-1155.
- Taylor JP, Hardy J, Fischbeck KH. Toxic proteins in neurodegenerative disease. Science. 2002;296(5575):1991–1995.
- Alves-Rodrigues A, Gregori L, Figueiredo-Pereira ME. Ubiquitin, cellular inclusions and their role in neurodegeneration. Trends Neurosci. 1998;21(12):516–520.
- Ciechanover A, Kwon YT. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp Mol Med. 2015;47(3):e147.
- Gadad BS, Britton GB, Rao KS. Targeting oligomers in neurodegenerative disorders: lessons from α-synuclein, tau, and amyloid-β peptide. J Alzheimers Dis. 2011;24(Suppl 2):223–232.
- Ross CA, Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med. 2004;10(S7):S10–7.
- Yerbury JJ, Ooi L, Dillin A, et al. Walking the tightrope: proteostasis and neurodegenerative disease. J Neurochem. 2016;137(4):489–505. DOI:https://doi.org/10.1111/jnc.13575.
- Corti O, Blomgren K, Poletti A, et al. Autophagy in neurodegeneration: new insights underpinning therapy for neurological diseases. J Neurochem. 2020;154(4):354–371. DOI:https://doi.org/10.1111/jnc.15002.
- Finkbeiner S. The autophagy lysosomal pathway and neurodegeneration. Cold Spring Harb Perspect Biol. 2020;12(3):3.
- Frake RA, Ricketts T, Menzies FM, et al. Autophagy and neurodegeneration. J Clin Invest. 2015;125(1):65–74. DOI:https://doi.org/10.1172/JCI73944.
- Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, et al. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 2014;26(12):2694–2701. DOI:https://doi.org/10.1016/j.cellsig.2014.08.019.
- Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27–42.
- Martini-Stoica H, Xu Y, Ballabio A, et al. The autophagy-lysosomal pathway in neurodegeneration: a TFEB perspective. Trends Neurosci. 2016;39(4):221–234. DOI:https://doi.org/10.1016/j.tins.2016.02.002.
- Menzies FM, Fleming A, Caricasole A, et al. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron. 2017;93(5):1015–1034.
- Menzies FM, Fleming A, Rubinsztein DC. Compromised autophagy and neurodegenerative diseases. Nat Rev Neurosci. 2015;16(6):345–357.
- Lorente Pons A, Higginbottom A, Cooper-Knock J, et al. Oligodendrocyte pathology exceeds axonal pathology in white matter in human amyotrophic lateral sclerosis. J Pathol. 2020;251(3):262–271. DOI:https://doi.org/10.1002/path.5455.
- Lippai M, Lőw P. The role of the selective adaptor p62 and ubiquitin-like proteins in autophagy. Biomed Res Int. 2014;2014:832704.
- Pankiv S, Clausen TH, Lamark T, et al. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem. 2007;282(33):24131–24145. DOI:https://doi.org/10.1074/jbc.M702824200.
- Lamark T, Svenning S, Johansen T. Regulation of selective autophagy: the p62/SQSTM1 paradigm. Essays Biochem. 2017;61(6):609–624.
- Sánchez-Martín P, Komatsu M. p62/SQSTM1 - steering the cell through health and disease. J Cell Sci. 2018;131(21):21.
- Long J, Garner TP, Pandya MJ, et al. Dimerisation of the UBA domain of p62 inhibits ubiquitin binding and regulates NF-kappaB signalling. J Mol Biol. 2010;396(1):178–194. DOI:https://doi.org/10.1016/j.jmb.2009.11.032.
- Isogai S, Morimoto D, Arita K, et al. Crystal structure of the ubiquitin-associated (UBA) domain of p62 and its interaction with ubiquitin. J Biol Chem. 2011;286(36):31864–31874. DOI:https://doi.org/10.1074/jbc.M111.259630.
- Lim J, Lachenmayer ML, Wu S, et al. Proteotoxic stress induces phosphorylation of p62/SQSTM1 by ULK1 to regulate selective autophagic clearance of protein aggregates. PLoS Genet. 2015;11(2):e1004987. DOI:https://doi.org/10.1371/journal.pgen.1004987.
- Pilli M, Arko-Mensah J, Ponpuak M, et al. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity. 2012;37(2):223–234. DOI:https://doi.org/10.1016/j.immuni.2012.04.015.
- Wurzer B, Zaffagnini G, Fracchiolla D, et al. Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy. Elife. 2015;4:e08941.
- Sun D, Wu R, Zheng J, et al. Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation. Cell Res. 2018;28(4):405–415. DOI:https://doi.org/10.1038/s41422-018-0017-7.
- Zaffagnini G, Savova A, Danieli A, et al. p62 filaments capture and present ubiquitinated cargos for autophagy. Embo J. 2018;37(5):5. DOI:https://doi.org/10.15252/embj.201798308.
- Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1–222.
- Mizushima N, Yoshimori T. How to interpret LC3 immunoblotting. Autophagy. 2007;3(6):542–545.
- Zheng YT, Shahnazari S, Brech A, et al. The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol. 2009;183(9):5909–5916. DOI:https://doi.org/10.4049/jimmunol.0900441.
- Deng H, Dodson MW, Huang H, et al. The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105(38):14503–14508. DOI:https://doi.org/10.1073/pnas.0803998105.
- Yang Y, Gehrke S, Imai Y, et al. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc Natl Acad Sci U S A. 2006;103(28):10793–10798. DOI:https://doi.org/10.1073/pnas.0602493103.
- Geisler S, Holmström KM, Skujat D, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12(2):119–131. DOI:https://doi.org/10.1038/ncb2012.
- Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2011;7(3):279–296.
- Moscat J, Diaz-Meco MT. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell. 2009;137(6):1001–1004.
- Sánchez-Martín P, Saito T, Komatsu M. p62/SQSTM1: ‘Jack of all trades’ in health and cancer. Febs J. 2019;286(1):8–23.
- Duran A, Amanchy R, Linares JF, et al. p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol Cell. 2011;44(1):134–146. DOI:https://doi.org/10.1016/j.molcel.2011.06.038.
- Linares JF, Duran A, Reina-Campos M, et al. Amino acid activation of mTORC1 by a PB1-domain-driven kinase complex cascade. Cell Rep. 2015;12(8):1339–1352. DOI:https://doi.org/10.1016/j.celrep.2015.07.045.
- Linares JF, Duran A, Yajima T, et al. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol Cell. 2013;51(3):283–296. DOI:https://doi.org/10.1016/j.molcel.2013.06.020.
- Myeku N, Figueiredo-Pereira ME. Dynamics of the degradation of ubiquitinated proteins by proteasomes and autophagy: association with sequestosome 1/p62. J Biol Chem. 2011;286(25):22426–22440.
- Sahani MH, Itakura E, Mizushima N. Expression of the autophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids. Autophagy. 2014;10(3):431–441.
- Seibenhener ML, Babu JR, Geetha T, et al. Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation. Mol Cell Biol. 2004;24(18):8055–8068. DOI:https://doi.org/10.1128/MCB.24.18.8055-8068.2004.
- Lee J, Kim HR, Quinley C, et al. Autophagy suppresses interleukin-1β (IL-1β) signaling by activation of p62 degradation via lysosomal and proteasomal pathways. J Biol Chem. 2012;287(6):4033–4040.
- Bellezza I, Giambanco I, Minelli A, et al. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta Mol Cell Res. 2018;1865(5):721–733. DOI:https://doi.org/10.1016/j.bbamcr.2018.02.010.
- Jain A, Lamark T, Sjøttem E, et al. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem. 2010;285(29):22576–22591. DOI:https://doi.org/10.1074/jbc.M110.118976.
- Jo C, Kim S, Cho SJ, et al. Sulforaphane induces autophagy through ERK activation in neuronal cells. FEBS Lett. 2014;588(17):3081–3088. DOI:https://doi.org/10.1016/j.febslet.2014.06.036.
- Komatsu M, Kurokawa H, Waguri S, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12(3):213–223. DOI:https://doi.org/10.1038/ncb2021.
- Kuusisto E, Suuronen T, Salminen A. Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells. Biochem Biophys Res Commun. 2001;280(1):223–228.
- Zatloukal K, Stumptner C, Fuchsbichler A, et al. p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol. 2002;160(1):255–263. DOI:https://doi.org/10.1016/S0002-9440(10)64369-6.
- Arai T, Nonaka T, Hasegawa M, et al. Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62. Neurosci Lett. 2003;342(1–2):41–44. DOI:https://doi.org/10.1016/S0304-3940(03)00216-7.
- Hiji M, Takahashi T, Fukuba H, et al. White matter lesions in the brain with frontotemporal lobar degeneration with motor neuron disease: TDP-43-immunopositive inclusions co-localize with p62, but not ubiquitin. Acta Neuropathol. 2008;116(2):183–191. DOI:https://doi.org/10.1007/s00401-008-0402-2.
- Mizuno Y, Amari M, Takatama M, et al. Immunoreactivities of p62, an ubiqutin-binding protein, in the spinal anterior horn cells of patients with amyotrophic lateral sclerosis. J Neurol Sci. 2006;249(1):13–18. DOI:https://doi.org/10.1016/j.jns.2006.05.060.
- Al-Sarraj S, King A, Troakes C, et al. p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS. Acta Neuropathol. 2011;122(6):691–702. DOI:https://doi.org/10.1007/s00401-011-0911-2.
- Mackenzie IR, Frick P, Neumann M. The neuropathology associated with repeat expansions in the C9ORF72 gene. Acta Neuropathol. 2014;127(3):347–357.
- Troakes C, Maekawa S, Wijesekera L, et al. An MND/ALS phenotype associated with C9orf72 repeat expansion: abundant p62-positive, TDP-43-negative inclusions in cerebral cortex, hippocampus and cerebellum but without associated cognitive decline. Neuropathology. 2012;32(5):505–514. DOI:https://doi.org/10.1111/j.1440-1789.2011.01286.x.
- Türk M, Haaker G, Winter L, et al. C9ORF72-ALS: P62- and ubiquitin-aggregation pathology in skeletal muscle. Muscle Nerve. 2014;50(3):454–455. DOI:https://doi.org/10.1002/mus.24283.
- Le Ber I, Camuzat A, Guerreiro R, et al. SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. JAMA Neurol. 2013;70(11):1403–1410. DOI:https://doi.org/10.1001/jamaneurol.2013.3849.
- Fecto F, Yan J, Vemula SP, et al. SQSTM1 mutations in familial and sporadic amyotrophic lateral sclerosis. Arch Neurol. 2011;68(11):1440–1446. DOI:https://doi.org/10.1001/archneurol.2011.250.
- Teyssou E, Takeda T, Lebon V, et al. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol. 2013;125(4):511–522.
- Laurin N, Brown JP, Morissette J, et al. Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet. 2002;70(6):1582–1588. DOI:https://doi.org/10.1086/340731.
- Rea SL, Majcher V, Searle MS, et al. SQSTM1 mutations–bridging Paget disease of bone and ALS/FTLD. Exp Cell Res. 2014;325(1):27–37. DOI:https://doi.org/10.1016/j.yexcr.2014.01.020.
- Gang Q, Bettencourt C, Machado PM, et al. Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Neurobiol Aging. 2016;47:218.e1–218.e9.
- Kim HJ, Kim NC, Wang YD, et al. Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS. Nature. 2013;495(7442):467–473. DOI:https://doi.org/10.1038/nature11922.
- Rea SL, Walsh JP, Layfield R, et al. New insights into the role of sequestosome 1/p62 mutant proteins in the pathogenesis of Paget’s disease of bone. Endocr Rev. 2013;34(4):501–524.
- Ichimura Y, Kumanomidou T, Sou YS, et al. Structural basis for sorting mechanism of p62 in selective autophagy. J Biol Chem. 2008;283(33):22847–22857. DOI:https://doi.org/10.1074/jbc.M802182200.
- Du Y, Wooten MC, Wooten MW. Oxidative damage to the promoter region of SQSTM1/p62 is common to neurodegenerative disease. Neurobiol Dis. 2009;35(2):302–310.
- Rubino E, Rainero I, Chiò A, et al. SQSTM1 mutations in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Neurology. 2012;79(15):1556–1562. DOI:https://doi.org/10.1212/WNL.0b013e31826e25df.
- Babu A, Wang Q, Muralidharan R, et al. Chitosan coated polylactic acid nanoparticle-mediated combinatorial delivery of cisplatin and siRNA/Plasmid DNA chemosensitizes cisplatin-resistant human ovarian cancer cells. Mol Pharm. 2014;11(8):2720–2733. DOI:https://doi.org/10.1021/mp500259e.
- Durán A, Serrano M, Leitges M, et al. The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Dev Cell. 2004;6(2):303–309. DOI:https://doi.org/10.1016/S1534-5807(03)00403-9.
- Rodriguez A, Durán A, Selloum M, et al. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metab. 2006;3(3):211–222. DOI:https://doi.org/10.1016/j.cmet.2006.01.011.
- Lattante S, De Calbiac H, Le Ber I, et al. Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD. Hum Mol Genet. 2015;24(6):1682–1690. DOI:https://doi.org/10.1093/hmg/ddu580.
- Daroszewska A, Van ‘T Hof RJ, Rojas JA, et al. A point mutation in the ubiquitin-associated domain of SQSMT1 is sufficient to cause a Paget’s disease-like disorder in mice. Hum Mol Genet. 2011;20(14):2734–2744. DOI:https://doi.org/10.1093/hmg/ddr172.
- Kurihara N, Hiruma Y, Zhou H, et al. Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease. J Clin Invest. 2007;117(1):133–142. DOI:https://doi.org/10.1172/JCI28267.
- Seibenhener ML, Zhao T, Du Y, et al. Behavioral effects of SQSTM1/p62 overexpression in mice: support for a mitochondrial role in depression and anxiety. Behav Brain Res. 2013;248:94–103.
- DeJesus-Hernandez M, Mackenzie IR, Boeve BF, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron. 2011;72(2):245–256. DOI:https://doi.org/10.1016/j.neuron.2011.09.011.
- Renton AE, Majounie E, Waite A, et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011;72(2):257–268. DOI:https://doi.org/10.1016/j.neuron.2011.09.010.
- Levine TP, Daniels RD, Gatta AT, et al. The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs. Bioinformatics. 2013;29(4):499–503. DOI:https://doi.org/10.1093/bioinformatics/bts725.
- Zhang D, Iyer LM, He F, et al. Discovery of Novel DENN Proteins: implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease. Front Genet. 2012;3:283.
- Farg MA, Sundaramoorthy V, Sultana JM, et al. C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum Mol Genet. 2014;23(13):3579–3595. DOI:https://doi.org/10.1093/hmg/ddu068.
- Almeida S, Gao FB. Lost & found: C9ORF72 and the autophagy pathway in ALS/FTD. Embo J. 2016;35(12):1251–1253.
- Amick J, Tharkeshwar AK, Amaya C, et al. WDR41 supports lysosomal response to changes in amino acid availability. Mol Biol Cell. 2018;29(18):2213–2227. DOI:https://doi.org/10.1091/mbc.E17-12-0703.
- Sellier C, Campanari ML, Julie Corbier C, et al. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. Embo J. 2016;35(12):1276–1297. DOI:https://doi.org/10.15252/embj.201593350.
- Sullivan PM, Zhou X, Robins AM, et al. The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. Acta Neuropathol Commun. 2016;4(1):51. DOI:https://doi.org/10.1186/s40478-016-0324-5.
- Yang M, Liang C, Swaminathan K, et al. A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy. Sci Adv. 2016;2(9):e1601167. DOI:https://doi.org/10.1126/sciadv.1601167.
- Goud B, M M. Small GTP-binding proteins and their role in transport. Curr Opin Cell Biol. 1991;3(4):626–633.
- Thomas JD, Zhang YJ, Wei YH, et al. Rab1A is an mTORC1 activator and a colorectal oncogene. Cancer Cell. 2014;26(5):754–769. DOI:https://doi.org/10.1016/j.ccell.2014.09.008.
- Webster CP, Smith EF, Bauer CS, et al. The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. Embo J. 2016;35(15):1656–1676. DOI:https://doi.org/10.15252/embj.201694401.
- Shi Y, Lin S, Staats KA, et al. Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons. Nat Med. 2018;24(3):313–325. DOI:https://doi.org/10.1038/nm.4490.
- Anor CJ, Xi Z, Zhang M, et al. Mutation analysis of C9orf72 in patients with corticobasal syndrome. Neurobiol Aging. 2015;36(10):2905.e1–5. DOI:https://doi.org/10.1016/j.neurobiolaging.2015.06.008.
- Beck J, Poulter M, Hensman D, et al. Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population. Am J Hum Genet. 2013;92(3):345–353. DOI:https://doi.org/10.1016/j.ajhg.2013.01.011.
- Cacace R, Van Cauwenberghe C, Bettens K, et al. C9orf72 G4C2 repeat expansions in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging. 2013;34(6):1712.e1–7. DOI:https://doi.org/10.1016/j.neurobiolaging.2012.12.019.
- Harms M, Benitez BA, Cairns N, et al. C9orf72 hexanucleotide repeat expansions in clinical Alzheimer disease. JAMA Neurol. 2013;70(6):736–741. DOI:https://doi.org/10.1001/2013.jamaneurol.537.
- Kostić VS, Dobričić V, Stanković I, et al. C9orf72 expansion as a possible genetic cause of Huntington disease phenocopy syndrome. J Neurol. 2014;261(10):1917–1921. DOI:https://doi.org/10.1007/s00415-014-7430-8.
- Lesage S, Le Ber I, Condroyer C, et al. C9orf72 repeat expansions are a rare genetic cause of parkinsonism. Brain. 2013;136(2):385–391. DOI:https://doi.org/10.1093/brain/aws357.
- Lindquist SG, Duno M, Batbayli M, et al. Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease. Clin Genet. 2013;83(3):279–283. DOI:https://doi.org/10.1111/j.1399-0004.2012.01903.x.
- Luigetti M, Quaranta D, Conte A, et al. Frontotemporal dementia, Parkinsonism and lower motor neuron involvement in a patient with C9ORF72 expansion. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14(1):66–69. DOI:https://doi.org/10.3109/17482968.2012.692383.
- O’Dowd S, Curtin D, Waite AJ, et al. C9ORF72 expansion in amyotrophic lateral sclerosis/frontotemporal dementia also causes parkinsonism. Mov Disord. 2012;27(8):1072–1074. DOI:https://doi.org/10.1002/mds.25022.
- Hensman Moss DJ, Poulter M, Beck J, et al. C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology. 2014;82(4):292–299. DOI:https://doi.org/10.1212/WNL.0000000000000061.
- Ash PE, Bieniek KF, Gendron TF, et al. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron. 2013;77(4):639–646. DOI:https://doi.org/10.1016/j.neuron.2013.02.004.
- Kwon I, Xiang S, Kato M, et al. Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells. Science. 2014;345(6201):1139–1145. DOI:https://doi.org/10.1126/science.1254917.
- Mori K, Arzberger T, Grässer FA, et al. Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol. 2013;126(6):881–893. DOI:https://doi.org/10.1007/s00401-013-1189-3.
- Wen X, Tan W, Westergard T, et al. Antisense proline-arginine RAN dipeptides linked to C9ORF72-ALS/FTD form toxic nuclear aggregates that initiate in vitro and in vivo neuronal death. Neuron. 2014;84(6):1213–1225. DOI:https://doi.org/10.1016/j.neuron.2014.12.010.
- Mackenzie IR, Arzberger T, Kremmer E, et al. Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations. Acta Neuropathol. 2013;126(6):859–879. DOI:https://doi.org/10.1007/s00401-013-1181-y.
- Mahoney CJ, Downey LE, Ridgway GR, et al. Longitudinal neuroimaging and neuropsychological profiles of frontotemporal dementia with C9ORF72 expansions. Alzheimers Res Ther. 2012;4(5):41. DOI:https://doi.org/10.1186/alzrt144.
- Mann DM, Rollinson S, Robinson A, et al. Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72. Acta Neuropathol Commun. 2013;1(1):68. DOI:https://doi.org/10.1186/2051-5960-1-68
- Boivin M, Pfister V, Gaucherot A, et al. Reduced autophagy upon C9ORF72 loss synergizes with dipeptide repeat protein toxicity in G4C2 repeat expansion disorders. Embo J. 2020;39(4):e100574. DOI:https://doi.org/10.15252/embj.2018100574.
- Zhu Q, Jiang J, Gendron TF, et al. Reduced C9ORF72 function exacerbates gain of toxicity from ALS/FTD-causing repeat expansion in C9orf72. Nat Neurosci. 2020;23(5):615–624. DOI:https://doi.org/10.1038/s41593-020-0619-5.
- Davidson Y, Robinson AC, Liu X, et al. Neurodegeneration in frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9orf72 is linked to TDP-43 pathology and not associated with aggregated forms of dipeptide repeat proteins. Neuropathol Appl Neurobiol. 2016;42(3):242–254. DOI:https://doi.org/10.1111/nan.12292.
- Gendron TF, Van Blitterswijk M, Bieniek KF, et al. Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers. Acta Neuropathol. 2015;130(4):559–573. DOI:https://doi.org/10.1007/s00401-015-1474-4.
- Gomez-Deza J, Lee YB, Troakes C, et al. Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration. Acta Neuropathol Commun. 2015;3(1):38. DOI:https://doi.org/10.1186/s40478-015-0218-y.
- Mackenzie IR, Frick P, Grässer FA, et al. Quantitative analysis and clinico-pathological correlations of different dipeptide repeat protein pathologies in C9ORF72 mutation carriers. Acta Neuropathol. 2015;130(6):845–861. DOI:https://doi.org/10.1007/s00401-015-1476-2.
- Almeida S, Gascon E, Tran H, et al. Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons. Acta Neuropathol. 2013;126(3):385–399. DOI:https://doi.org/10.1007/s00401-013-1149-y.
- Ji YJ, Ugolino J, Brady NR, et al. Systemic deregulation of autophagy upon loss of ALS- and FTD-linked C9orf72. Autophagy. 2017;13(7):1254–1255. DOI:https://doi.org/10.1080/15548627.2017.1299312.
- Ugolino J, Ji YJ, Conchina K, et al. Loss of C9orf72 Enhances Autophagic Activity via Deregulated mTOR and TFEB Signaling. PLoS Genet. 2016;12(11):e1006443. DOI:https://doi.org/10.1371/journal.pgen.1006443.
- Madill M, McDonagh K, Ma J, et al. Amyotrophic lateral sclerosis patient iPSC-derived astrocytes impair autophagy via non-cell autonomous mechanisms. Mol Brain. 2017;10(1):22. DOI:https://doi.org/10.1186/s13041-017-0300-4.
- Ciura S, Lattante S, Le Ber I, et al. Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis. Ann Neurol. 2013;74(2):180–187. DOI:https://doi.org/10.1002/ana.23946.
- Therrien M, Rouleau GA, Dion PA, et al. Deletion of C9ORF72 results in motor neuron degeneration and stress sensitivity in C. elegans. PLoS One. 2013;8(12):e83450. DOI:https://doi.org/10.1371/journal.pone.0083450.
- Atanasio A, Decman V, White D, et al. C9orf72 ablation causes immune dysregulation characterized by leukocyte expansion, autoantibody production, and glomerulonephropathy in mice. Sci Rep. 2016;6(1):23204. DOI:https://doi.org/10.1038/srep23204.
- Burberry A, Suzuki N, Wang JY, et al. Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease. Sci Transl Med. 2016;8(347):347ra93. DOI:https://doi.org/10.1126/scitranslmed.aaf6038.
- O’Rourke JG, Bogdanik L, Muhammad A, et al. C9orf72 BAC transgenic mice display typical pathologic features of ALS/FTD. Neuron. 2015;88(5):892–901. DOI:https://doi.org/10.1016/j.neuron.2015.10.027.
- Sudria-Lopez E, Koppers M, De Wit M, et al. Full ablation of C9orf72 in mice causes immune system-related pathology and neoplastic events but no motor neuron defects. Acta Neuropathol. 2016;132(1):145–147. DOI:https://doi.org/10.1007/s00401-016-1581-x.
- Devlin AC, Burr K, Borooah S, et al. Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability. Nat Commun. 2015;6(1):5999. DOI:https://doi.org/10.1038/ncomms6999.
- Wainger BJ, Kiskinis E, Mellin C, et al. Intrinsic membrane hyperexcitability of amyotrophic lateral sclerosis patient-derived motor neurons. Cell Rep. 2014;7(1):1–11. DOI:https://doi.org/10.1016/j.celrep.2014.03.019.
- Donnelly CJ, Zhang PW, Pham JT, et al. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron. 2013;80(2):415–428. DOI:https://doi.org/10.1016/j.neuron.2013.10.015.
- Selvaraj BT, Livesey MR, Zhao C, et al. C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca(2+)-permeable AMPA receptor-mediated excitotoxicity. Nat Commun. 2018;9(1):347. DOI:https://doi.org/10.1038/s41467-017-02729-0.
- Oakes JA, Davies MC, Collins MO. TBK1: a new player in ALS linking autophagy and neuroinflammation. Mol Brain. 2017;10(1):5.
- Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science. 2015;347(6220):1260419.
- Richter B, Sliter DA, Herhaus L, et al. Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A. 2016;113(15):4039–4044. DOI:https://doi.org/10.1073/pnas.1523926113.
- Loo YM, Gale M Jr. Immune signaling by RIG-I-like receptors. Immunity. 2011;34(5):680–692.
- Wild P, Farhan H, McEwan DG, et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science. 2011;333(6039):228–233. DOI:https://doi.org/10.1126/science.1205405.
- Jung J, Nayak A, Schaeffer V, et al. Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. Elife. 2017;6:6.
- Nakashima H, Nguyen T, Goins WF, et al. Interferon-stimulated gene 15 (ISG15) and ISG15-linked proteins can associate with members of the selective autophagic process, histone deacetylase 6 (HDAC6) and SQSTM1/p62. J Biol Chem. 2015;290(3):1485–1495. DOI:https://doi.org/10.1074/jbc.M114.593871.
- Xu D, Zhang T, Xiao J, et al. Modification of BECN1 by ISG15 plays a crucial role in autophagy regulation by type I IFN/interferon. Autophagy. 2015;11(4):617–628. DOI:https://doi.org/10.1080/15548627.2015.1023982.
- Goncalves A, Bürckstümmer T, Dixit E, et al. Functional dissection of the TBK1 molecular network. PLoS One. 2011;6(9):e23971. DOI:https://doi.org/10.1371/journal.pone.0023971.
- Kim JY, Beg AA, Haura EB, et al. IKKϵ and TBK1, as novel therapeutic targets in the treatment of non-small cell lung cancer. Expert Opin Ther Targets. 2013;17(10):1109–1112.
- Awadalla MS, Fingert JH, Roos BE, et al. Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma. Am J Ophthalmol. 2015;159(1):124–30.e1. DOI:https://doi.org/10.1016/j.ajo.2014.09.044.
- Ritch R, Darbro B, Menon G, et al. TBK1 gene duplication and normal-tension glaucoma. JAMA Ophthalmol. 2014;132(5):544–548. DOI:https://doi.org/10.1001/jamaophthalmol.2014.104.
- Herman M, Ciancanelli M, Ou YH, et al. Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood. J Exp Med. 2012;209(9):1567–1582. DOI:https://doi.org/10.1084/jem.20111316.
- Cirulli ET, Lasseigne BN, Petrovski S, et al. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science. 2015;347(6229):1436–1441. DOI:https://doi.org/10.1126/science.aaa3650.
- Freischmidt A, Wieland T, Richter B, et al. Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci. 2015;18(5):631–636. DOI:https://doi.org/10.1038/nn.4000.
- Gijselinck I, Van Mossevelde S, Van Der Zee J, et al. Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort. Neurology. 2015;85(24):2116–2125. DOI:https://doi.org/10.1212/WNL.0000000000002220.
- Le Ber I, De Septenville A, Millecamps S, et al. TBK1 mutation frequencies in French frontotemporal dementia and amyotrophic lateral sclerosis cohorts. Neurobiol Aging. 2015;36(11):3116.e5–3116.e8. DOI:https://doi.org/10.1016/j.neurobiolaging.2015.08.009.
- Pottier C, Bieniek KF, Finch N, et al. Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease. Acta Neuropathol. 2015;130(1):77–92. DOI:https://doi.org/10.1007/s00401-015-1436-x.
- Gijselinck I, Van Mossevelde S, Van Der Zee J, et al. The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter. Mol Psychiatry. 2016;21(8):1112–1124. DOI:https://doi.org/10.1038/mp.2015.159.
- Van Mossevelde S, Van Der Zee J, Gijselinck I, et al. Clinical features of TBK1 carriers compared with C9orf72, GRN and non-mutation carriers in a Belgian cohort. Brain. 2016;139(2):452–467. DOI:https://doi.org/10.1093/brain/awv358.
- Lazarou M, Sliter DA, Kane LA, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524(7565):309–314. DOI:https://doi.org/10.1038/nature14893.
- Moore AS, Holzbaur EL. Spatiotemporal dynamics of autophagy receptors in selective mitophagy. Autophagy. 2016;12(10):1956–1957.
- Brenner D, Sieverding K, Bruno C, et al. Heterozygous Tbk1 loss has opposing effects in early and late stages of ALS in mice. J Exp Med. 2019;216(2):267–278.
- Gerbino V, Kaunga E, Ye J, et al. The Loss of TBK1 Kinase Activity in Motor Neurons or in All Cell Types Differentially Impacts ALS Disease Progression in SOD1 Mice. Neuron. 2020;106(5):789–805.e5.
- Yu J, Zhou X, Chang M, et al. Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation. Nat Commun. 2015;6(1):6074. DOI:https://doi.org/10.1038/ncomms7074.
- Komine O, Yamanaka K. Neuroinflammation in motor neuron disease. Nagoya J Med Sci. 2015;77(4):537–549.
- Walters KJ, Goh AM, Wang Q, et al. Ubiquitin family proteins and their relationship to the proteasome: a structural perspective. Biochim Biophys Acta. 2004;1695(1–3):73–87. DOI:https://doi.org/10.1016/j.bbamcr.2004.10.005.
- N’Diaye EN, Kajihara KK, Hsieh I, et al. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO Rep. 2009;10(2):173–179. DOI:https://doi.org/10.1038/embor.2008.238.
- Rothenberg C, Srinivasan D, Mah L, et al. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Hum Mol Genet. 2010;19(16):3219–3232. DOI:https://doi.org/10.1093/hmg/ddq231.
- Deng HX, Chen W, Hong ST, et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature. 2011;477(7363):211–215. DOI:https://doi.org/10.1038/nature10353.
- Millecamps S, Corcia P, Cazeneuve C, et al. Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33(4):839.e1–3. DOI:https://doi.org/10.1016/j.neurobiolaging.2011.11.010.
- Daoud H, Suhail H, Szuto A, et al. UBQLN2 mutations are rare in French and French-Canadian amyotrophic lateral sclerosis. Neurobiol Aging. 2012;33(9):2230.e1–2230.e5. DOI:https://doi.org/10.1016/j.neurobiolaging.2012.03.015.
- Mizusawa H, Nakamura H, Wakayama I, et al. Skein-like inclusions in the anterior horn cells in motor neuron disease. J Neurol Sci. 1991;105(1):14–21. DOI:https://doi.org/10.1016/0022-510X(91)90112-K.
- Osaka M, Ito D, Suzuki N. Disturbance of proteasomal and autophagic protein degradation pathways by amyotrophic lateral sclerosis-linked mutations in ubiquilin 2. Biochem Biophys Res Commun. 2016;472(2):324–331.
- Ceballos-Diaz C, Rosario AM, Park HJ, et al. Viral expression of ALS-linked ubiquilin-2 mutants causes inclusion pathology and behavioral deficits in mice. Mol Neurodegener. 2015;10(1):25. DOI:https://doi.org/10.1186/s13024-015-0026-7
- Picher-Martel V, Dutta K, Phaneuf D, et al. Ubiquilin-2 drives NF-κB activity and cytosolic TDP-43 aggregation in neuronal cells. Mol Brain. 2015;8(1):71. DOI:https://doi.org/10.1186/s13041-015-0162-6.
- Wu Q, Liu M, Huang C, et al. Pathogenic Ubqln2 gains toxic properties to induce neuron death. Acta Neuropathol. 2015;129(3):417–428. DOI:https://doi.org/10.1007/s00401-014-1367-y.
- Şentürk M, Lin G, Zuo Z, et al. Ubiquilins regulate autophagic flux through mTOR signalling and lysosomal acidification. Nat Cell Biol. 2019;21(3):384–396. DOI:https://doi.org/10.1038/s41556-019-0281-x.
- Wu JJ, Cai A, Greenslade JE, et al. ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function. Proc Natl Acad Sci U S A. 2020;117(26):15230–15241. DOI:https://doi.org/10.1073/pnas.1917371117.
- Yang W, Hamilton JL, Kopil C, et al. Current and projected future economic burden of Parkinson’s disease in the U. S NPJ Parkinsons Dis. 2020;6(1):15. DOI:https://doi.org/10.1038/s41531-020-0117-1
- Dormann D, Madl T, Valori CF, et al. Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. Embo J. 2012;31(22):4258–4275. DOI:https://doi.org/10.1038/emboj.2012.261.
- Huey ED, Ferrari R, Moreno JH, et al. FUS and TDP43 genetic variability in FTD and CBS. Neurobiol Aging. 2012;33(5):1016.e9–17. DOI:https://doi.org/10.1016/j.neurobiolaging.2011.08.004.
- Ling SC, Polymenidou M, Cleveland DW. Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis. Neuron. 2013;79(3):416–438.
- Ryu HH, Jun MH, Min KJ, et al. Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons. Neurobiol Aging. 2014;35(12):2822–2831. DOI:https://doi.org/10.1016/j.neurobiolaging.2014.07.026.
- Marrone L, Poser I, Casci I, et al. Isogenic FUS-eGFP iPSC reporter lines enable quantification of FUS stress granule pathology that is rescued by drugs inducing autophagy. Stem Cell Reports. 2018;10(2):375–389. DOI:https://doi.org/10.1016/j.stemcr.2017.12.018.
- Arenas A, Kuang L, Zhang J, et al. FUS regulates autophagy by mediating the transcription of genes critical to the autophagosome formation. J Neurochem. 2020;157(3):752–763.
- Halawani D, Latterich M. p97: the cell’s molecular purgatory?. Mol Cell. 2006;22(6):713–717.
- Kakizuka A. Roles of VCP in human neurodegenerative disorders. Biochem Soc Trans. 2008;36(1):105–108.
- Watts GD, Wymer J, Kovach MJ, et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet. 2004;36(4):377–381. DOI:https://doi.org/10.1038/ng1332.
- DeJesus-Hernandez M, Desaro P, Johnston A, et al. Novel p.Ile151Val mutation in VCP in a patient of African American descent with sporadic ALS. Neurology. 2011;77(11):1102–1103.
- Koppers M, Groen EJ, Van Vught PW, et al. Screening for rare variants in the coding region of ALS-associated genes at 9p21.2 and 19p13.3. Neurobiol Aging. 2013;34(5):1518.e5–7. DOI:https://doi.org/10.1016/j.neurobiolaging.2012.09.018.
- Johnson JO, Mandrioli J, Benatar M, et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron. 2010;68(5):857–864. DOI:https://doi.org/10.1016/j.neuron.2010.11.036.
- Custer SK, Neumann M, Lu H, et al. Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone. Hum Mol Genet. 2010;19(9):1741–1755. DOI:https://doi.org/10.1093/hmg/ddq050.
- Hübbers CU, Clemen CS, Kesper K, et al. Pathological consequences of VCP mutations on human striated muscle. Brain. 2007;130(2):381–393. DOI:https://doi.org/10.1093/brain/awl238.
- Ju JS, Fuentealba RA, Miller SE, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol. 2009;187(6):875–888. DOI:https://doi.org/10.1083/jcb.200908115.
- Schröder R, Watts GD, Mehta SG, et al. Mutant valosin-containing protein causes a novel type of frontotemporal dementia. Ann Neurol. 2005;57(3):457–461. DOI:https://doi.org/10.1002/ana.20407.
- Nalbandian A, Llewellyn KJ, Kitazawa M, et al. The homozygote VCP(R155H/R155H) mouse model exhibits accelerated human VCP-associated disease pathology. PLoS One. 2012;7(9):e46308.
- Tresse E, Salomons FA, Vesa J, et al. VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy. 2010;6(2):217–227. DOI:https://doi.org/10.4161/auto.6.2.11014.
- Nalbandian A, Nguyen C, Katheria V, et al. Exercise training reverses skeletal muscle atrophy in an experimental model of VCP disease. PLoS One. 2013;8(10):e76187. DOI:https://doi.org/10.1371/journal.pone.0076187.
- Yin HZ, Nalbandian A, Hsu CI, et al. Slow development of ALS-like spinal cord pathology in mutant valosin-containing protein gene knock-in mice. Cell Death Dis. 2012;3(8):e374. DOI:https://doi.org/10.1038/cddis.2012.115.
- Hall CE, Yao Z, Choi M, et al. Progressive motor neuron pathology and the role of astrocytes in a human stem cell model of VCP-related ALS. Cell Rep. 2017;19(9):1739–1749. DOI:https://doi.org/10.1016/j.celrep.2017.05.024.
- Kachaner D, Génin P, Laplantine E, et al. Toward an integrative view of Optineurin functions. Cell Cycle. 2012;11(15):2808–2818. DOI:https://doi.org/10.4161/cc.20946.
- Korac J, Schaeffer V, Kovacevic I, et al. Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J Cell Sci. 2013;126(2):580–592. DOI:https://doi.org/10.1242/jcs.114926.
- Stolz A, Ernst A, Dikic I. Cargo recognition and trafficking in selective autophagy. Nat Cell Biol. 2014;16(6):495–501.
- Wong YC, Holzbaur EL. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A. 2014;111(42):E4439–48.
- Liu Z, Chen P, Gao H, et al. Ubiquitylation of autophagy receptor optineurin by HACE1 activates selective autophagy for tumor suppression. Cancer Cell. 2014;26(1):106–120. DOI:https://doi.org/10.1016/j.ccr.2014.05.015.
- Maruyama H, Morino H, Ito H, et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature. 2010;465(7295):223–226. DOI:https://doi.org/10.1038/nature08971.
- Evans CS, Holzbaur EL. Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons. Elife. 2020;9:9.
- Sako W, Ito H, Yoshida M, et al. Nuclear factor κ B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations. Clin Neuropathol. 2012;31(6):418–423. DOI:https://doi.org/10.5414/NP300493.
- Akizuki M, Yamashita H, Uemura K, et al. Optineurin suppression causes neuronal cell death via NF-κB pathway. J Neurochem. 2013;126(6):699–704. DOI:https://doi.org/10.1111/jnc.12326.
- Ghazi-Tabatabai S, Obita T, Pobbati AV, et al. Evolution and assembly of ESCRTs. Biochem Soc Trans. 2009;37(1):151–155. DOI:https://doi.org/10.1042/BST0370151.
- Odorizzi G. Membrane manipulations by the ESCRT machinery. F1000Res. 2015;4(F1000 Faculty Rev):516.
- Skibinski G, Parkinson NJ, Brown JM, et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet. 2005;37(8):806–808. DOI:https://doi.org/10.1038/ng1609.
- Van Der Zee J, Urwin H, Engelborghs S, et al. CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro. Hum Mol Genet. 2008;17(2):313–322. DOI:https://doi.org/10.1093/hmg/ddm309.
- Cox LE, Ferraiuolo L, Goodall EF, et al. Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS). PLoS One. 2010;5(3):e9872. DOI:https://doi.org/10.1371/journal.pone.0009872.
- Parkinson N, Ince PG, Smith MO, et al. ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology. 2006;67(6):1074–1077. DOI:https://doi.org/10.1212/01.wnl.0000231510.89311.8b.
- Filimonenko M, Stuffers S, Raiborg C, et al. Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol. 2007;179(3):485–500. DOI:https://doi.org/10.1083/jcb.200702115.
- Lee JA, Beigneux A, Ahmad ST, et al. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol. 2007;17(18):1561–1567. DOI:https://doi.org/10.1016/j.cub.2007.07.029.
- Clayton EL, Mancuso R, Nielsen TT, et al. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation. Hum Mol Genet. 2017;26(5):873–887. DOI:https://doi.org/10.1093/hmg/ddx003.
- Ghazi-Noori S, Froud KE, Mizielinska S, et al. Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice. Brain. 2012;135(3):819–832. DOI:https://doi.org/10.1093/brain/aws006.
- Clayton EL, Mizielinska S, Edgar JR, et al. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology. Acta Neuropathol. 2015;130(4):511–523. DOI:https://doi.org/10.1007/s00401-015-1475-3.
- Sasaki S. Autophagy in spinal cord motor neurons in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 2011;70(5):349–359.
- Arai T, Hasegawa M, Akiyama H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun. 2006;351(3):602–611. DOI:https://doi.org/10.1016/j.bbrc.2006.10.093.
- Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006;314(5796):130–133. DOI:https://doi.org/10.1126/science.1134108.
- Ying Z, Xia Q, Hao Z, et al. TARDBP/TDP-43 regulates autophagy in both MTORC1-dependent and MTORC1-independent manners. Autophagy. 2016;12(4):707–708. DOI:https://doi.org/10.1080/15548627.2016.1151596.
- Ito Y, Yamada M, Tanaka H, et al. Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice. Neurobiol Dis. 2009;36(3):470–476. DOI:https://doi.org/10.1016/j.nbd.2009.08.013.
- Atkin JD, Farg MA, Walker AK, et al. Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis. Neurobiol Dis. 2008;30(3):400–407. DOI:https://doi.org/10.1016/j.nbd.2008.02.009.
- Sasaki S. Endoplasmic reticulum stress in motor neurons of the spinal cord in sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol. 2010;69(4):346–355.
- Ilieva EV, Ayala V, Jové M, et al. Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis. Brain. 2007;130(Pt 12):3111–3123. DOI:https://doi.org/10.1093/brain/awm190.
- Atsumi T. The ultrastructure of intramuscular nerves in amyotrophic lateral sclerosis. Acta Neuropathol. 1981;55(3):193–198.
- Chung MJ, Suh YL. Ultrastructural changes of mitochondria in the skeletal muscle of patients with amyotrophic lateral sclerosis. Ultrastruct Pathol. 2002;26(1):3–7.
- Napoli L, Crugnola V, Lamperti C, et al. Ultrastructural mitochondrial abnormalities in patients with sporadic amyotrophic lateral sclerosis. Arch Neurol. 2011;68(12):1612–1613. DOI:https://doi.org/10.1001/archneur.68.12.1612.
- Sasaki S, Iwata M. Ultrastructural study of synapses in the anterior horn neurons of patients with amyotrophic lateral sclerosis. Neurosci Lett. 1996;204(1–2):53–56.
- Wiedemann FR, Winkler K, Kuznetsov AV, et al. Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci. 1998;156(1):65–72. DOI:https://doi.org/10.1016/S0022-510X(98)00008-2.
- Deng HX, Bigio EH, Zhai H, et al. Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations. Arch Neurol. 2011;68(8):1057–1061. DOI:https://doi.org/10.1001/archneurol.2011.178.
- Li C, Ji Y, Tang L, et al. Optineurin mutations in patients with sporadic amyotrophic lateral sclerosis in China. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(7–8):485–489. DOI:https://doi.org/10.3109/21678421.2015.1089909.
- Toth RP, Atkin JD. Dysfunction of optineurin in amyotrophic lateral sclerosis and glaucoma. Front Immunol. 2018;9:1017.
- Yang L, Cheng Y, Jia X, et al. Four novel optineurin mutations in patients with sporadic amyotrophic lateral sclerosis in Mainland China. Neurobiol Aging. 2021;97:149.e1–149.e8.
- Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet. 2008;40(5):572–574. DOI:https://doi.org/10.1038/ng.132.
- Sreedharan J, Blair IP, Tripathi VB, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008;319(5870):1668–1672. DOI:https://doi.org/10.1126/science.1154584.
- Van Deerlin VM, Leverenz JB, Bekris LM, et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 2008;7(5):409–416. DOI:https://doi.org/10.1016/S1474-4422(08)70071-1.
- Yokoseki A, Shiga A, Tan CF, et al. TDP-43 mutation in familial amyotrophic lateral sclerosis. Ann Neurol. 2008;63(4):538–542. DOI:https://doi.org/10.1002/ana.21392.
- Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362(6415):59–62. DOI:https://doi.org/10.1038/362059a0.
- Sea K, Sohn SH, Durazo A, et al. Insights into the role of the unusual disulfide bond in copper-zinc superoxide dismutase. J Biol Chem. 2015;290(4):2405–2418. DOI:https://doi.org/10.1074/jbc.M114.588798.
- Zou ZY, Zhou ZR, Che CH, et al. Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2017;88(7):540–549. DOI:https://doi.org/10.1136/jnnp-2016-315018.
- Barmada SJ, Skibinski G, Korb E, et al. Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis. J Neurosci. 2010;30(2):639–649. DOI:https://doi.org/10.1523/JNEUROSCI.4988-09.2010.
- Bilican B, Serio A, Barmada SJ, et al. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. Proc Natl Acad Sci U S A. 2012;109(15):5803–5808. DOI:https://doi.org/10.1073/pnas.1202922109.
- Serio A, Bilican B, Barmada SJ, et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proc Natl Acad Sci U S A. 2013;110(12):4697–4702. DOI:https://doi.org/10.1073/pnas.1300398110.
- Huang SL, Wu LS, Lee M, et al. A robust TDP-43 knock-in mouse model of ALS. Acta Neuropathol Commun. 2020;8(1):3. DOI:https://doi.org/10.1186/s40478-020-0881-5.
- Stallings NR, Puttaparthi K, Luther CM, et al. Progressive motor weakness in transgenic mice expressing human TDP-43. Neurobiol Dis. 2010;40(2):404–414. DOI:https://doi.org/10.1016/j.nbd.2010.06.017.
- Xu YF, Gendron TF, Zhang YJ, et al. Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice. J Neurosci. 2010;30(32):10851–10859. DOI:https://doi.org/10.1523/JNEUROSCI.1630-10.2010.
- Wils H, Kleinberger G, Janssens J, et al. TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A. 2010;107(8):3858–3863. DOI:https://doi.org/10.1073/pnas.0912417107.
- Shan X, Chiang PM, Price DL, et al. Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice. Proc Natl Acad Sci U S A. 2010;107(37):16325–16330. DOI:https://doi.org/10.1073/pnas.1003459107.
- Tsai KJ, Yang CH, Fang YH, et al. Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. J Exp Med. 2010;207(8):1661–1673. DOI:https://doi.org/10.1084/jem.20092164.
- Igaz LM, Kwong LK, Lee EB, et al. Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice. J Clin Invest. 2011;121(2):726–738. DOI:https://doi.org/10.1172/JCI44867.
- Tian T, Huang C, Tong J, et al. TDP-43 potentiates alpha-synuclein toxicity to dopaminergic neurons in transgenic mice. Int J Biol Sci. 2011;7(2):234–243. DOI:https://doi.org/10.7150/ijbs.7.234.
- Swarup V, Phaneuf D, Bareil C, et al. Pathological hallmarks of amyotrophic lateral sclerosis/frontotemporal lobar degeneration in transgenic mice produced with TDP-43 genomic fragments. Brain. 2011;134(9):2610–2626. DOI:https://doi.org/10.1093/brain/awr159.
- Cannon A, Yang B, Knight J, et al. Neuronal sensitivity to TDP-43 overexpression is dependent on timing of induction. Acta Neuropathol. 2012;123(6):807–823.
- Arnold ES, Ling SC, Huelga SC, et al. ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43. Proc Natl Acad Sci U S A. 2013;110(8):E736–45. DOI:https://doi.org/10.1073/pnas.1222809110.
- Zhou H, Huang C, Chen H, et al. Transgenic rat model of neurodegeneration caused by mutation in the TDP gene. PLoS Genet. 2010;6(3):e1000887. DOI:https://doi.org/10.1371/journal.pgen.1000887.
- Uchida A, Sasaguri H, Kimura N, et al. Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43. Brain. 2012;135(3):833–846. DOI:https://doi.org/10.1093/brain/awr348.
- Dayton RD, Wang DB, Cain CD, et al. Frontotemporal lobar degeneration-related proteins induce only subtle memory-related deficits when bilaterally overexpressed in the dorsal hippocampus. Exp Neurol. 2012;233(2):807–814. DOI:https://doi.org/10.1016/j.expneurol.2011.12.002.
- Herman AM, Khandelwal PJ, Rebeck GW, et al. Wild type TDP-43 induces neuro-inflammation and alters APP metabolism in lentiviral gene transfer models. Exp Neurol. 2012;235(1):297–305. DOI:https://doi.org/10.1016/j.expneurol.2012.02.011.
- Tatom JB, Wang DB, Dayton RD, et al. Mimicking aspects of frontotemporal lobar degeneration and Lou Gehrig’s disease in rats via TDP-43 overexpression. Mol Ther. 2009;17(4):607–613. DOI:https://doi.org/10.1038/mt.2009.3.
- Wang DB, Dayton RD, Henning PP, et al. Expansive gene transfer in the rat CNS rapidly produces amyotrophic lateral sclerosis relevant sequelae when TDP-43 is overexpressed. Mol Ther. 2010;18(12):2064–2074. DOI:https://doi.org/10.1038/mt.2010.191.
- Dayton RD, Gitcho MA, Orchard EA, et al. Selective forelimb impairment in rats expressing a pathological TDP-43 25 kDa C-terminal fragment to mimic amyotrophic lateral sclerosis. Mol Ther. 2013;21(7):1324–1334. DOI:https://doi.org/10.1038/mt.2013.88.
- Caccamo A, Majumder S, Oddo S. Cognitive decline typical of frontotemporal lobar degeneration in transgenic mice expressing the 25-kDa C-terminal fragment of TDP-43. Am J Pathol. 2012;180(1):293–302.
- Wegorzewska I, Bell S, Cairns NJ, et al. TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci U S A. 2009;106(44):18809–18814. DOI:https://doi.org/10.1073/pnas.0908767106.
- Xu YF, Zhang YJ, Lin WL, et al. Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice. Mol Neurodegener. 2011;6(1):73. DOI:https://doi.org/10.1186/1750-1326-6-73
- Janssens J, Wils H, Kleinberger G, et al. Overexpression of ALS-associated p.M337V human TDP-43 in mice worsens disease features compared to wild-type human TDP-43 mice. Mol Neurobiol. 2013;48(1):22–35.
- Huang C, Tong J, Bi F, et al. Mutant TDP-43 in motor neurons promotes the onset and progression of ALS in rats. J Clin Invest. 2012;122(1):107–118. DOI:https://doi.org/10.1172/JCI59130.
- Chiang PM, Ling J, Jeong YH, et al. Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc Natl Acad Sci U S A. 2010;107(37):16320–16324. DOI:https://doi.org/10.1073/pnas.1002176107.
- Iguchi Y, Katsuno M, Niwa J, et al. Loss of TDP-43 causes age-dependent progressive motor neuron degeneration. Brain. 2013;136(5):1371–1382. DOI:https://doi.org/10.1093/brain/awt029.
- Kraemer BC, Schuck T, Wheeler JM, et al. Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis. Acta Neuropathol. 2010;119(4):409–419. DOI:https://doi.org/10.1007/s00401-010-0659-0.
- Sephton CF, Good SK, Atkin S, et al. TDP-43 is a developmentally regulated protein essential for early embryonic development. J Biol Chem. 2010;285(9):6826–6834. DOI:https://doi.org/10.1074/jbc.M109.061846.
- Wu LS, Cheng WC, Hou SC, et al. TDP-43, a neuro-pathosignature factor, is essential for early mouse embryogenesis. Genesis. 2010;48(1):56–62. DOI:https://doi.org/10.1002/dvg.20584.
- Wu LS, Cheng WC, Shen CK. Targeted depletion of TDP-43 expression in the spinal cord motor neurons leads to the development of amyotrophic lateral sclerosis-like phenotypes in mice. J Biol Chem. 2012;287(33):27335–27344.
- Wegorzewska I, Baloh RHTDP. 43-based animal models of neurodegeneration: new insights into ALS pathology and pathophysiology. Neurodegener Dis. 2011;8(4):262–274.
- Baralle M, Buratti E, Baralle FE. The role of TDP-43 in the pathogenesis of ALS and FTLD. Biochem Soc Trans. 2013;41(6):1536–1540.
- Casci I, Pandey UB. A fruitful endeavor: modeling ALS in the fruit fly. Brain Res. 2015;1607:47–74.
- Chen H, Kankel MW, Su SC, et al. Exploring the genetics and non-cell autonomous mechanisms underlying ALS/FTLD. Cell Death Differ. 2018;25(4):648–662. DOI:https://doi.org/10.1038/s41418-018-0060-4.
- Liu YC, Chiang PM, Tsai KJ. Disease animal models of TDP-43 proteinopathy and their pre-clinical applications. Int J Mol Sci. 2013;14(10):20079–20111.
- Tan RH, Ke YD, Ittner LM, et al. ALS/FTLD: experimental models and reality. Acta Neuropathol. 2017;133(2):177–196. DOI:https://doi.org/10.1007/s00401-016-1666-6.
- Hetz C, Thielen P, Matus S, et al. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev. 2009;23(19):2294–2306. DOI:https://doi.org/10.1101/gad.1830709.
- Rudnick ND, Griffey CJ, Guarnieri P, et al. Distinct roles for motor neuron autophagy early and late in the SOD1(G93A) mouse model of ALS. Proc Natl Acad Sci U S A. 2017;114(39):E8294–e8303. DOI:https://doi.org/10.1073/pnas.1704294114.
- Morimoto N, Nagai M, Ohta Y, et al. Increased autophagy in transgenic mice with a G93A mutant SOD1 gene. Brain Res. 2007;1167:112–117.
- Zhang X, Li L, Chen S, et al. Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Autophagy. 2011;7(4):412–425. DOI:https://doi.org/10.4161/auto.7.4.14541.
- Gong YH, Parsadanian AS, Andreeva A, et al. Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J Neurosci. 2000;20(2):660–665. DOI:https://doi.org/10.1523/JNEUROSCI.20-02-00660.2000.
- Vargas MR, Johnson DA, Sirkis DW, et al. Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J Neurosci. 2008;28(50):13574–13581. DOI:https://doi.org/10.1523/JNEUROSCI.4099-08.2008.
- Julien JP, Kriz J. Transgenic mouse models of amyotrophic lateral sclerosis. Biochim Biophys Acta. 2006;1762(11–12):1013–1024.
- Morrice JR, Gregory-Evans CY, Shaw CA. Animal models of amyotrophic lateral sclerosis: a comparison of model validity. Neural Regen Res. 2018;13(12):2050–2054.
- Philips T, Rothstein JD. Rodent models of amyotrophic lateral sclerosis. Curr Protoc Pharmacol. 2015;69(1):5.67.1–5.67.21.
- Van Damme P, Robberecht W, Van Den Bosch L. and Van Den Bosch L. Modelling amyotrophic lateral sclerosis: progress and possibilities. Dis Model Mech. 2017;10(5):537–549.
- Nishihira Y, Tan CF, Onodera O, et al. Sporadic amyotrophic lateral sclerosis: two pathological patterns shown by analysis of distribution of TDP-43-immunoreactive neuronal and glial cytoplasmic inclusions. Acta Neuropathol. 2008;116(2):169–182. DOI:https://doi.org/10.1007/s00401-008-0385-z.
- Zhang H, Tan CF, Mori F, et al. TDP-43-immunoreactive neuronal and glial inclusions in the neostriatum in amyotrophic lateral sclerosis with and without dementia. Acta Neuropathol. 2008;115(1):115–122. DOI:https://doi.org/10.1007/s00401-007-0285-7.
- Papadeas ST, Kraig SE, O’Banion C, et al. Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neuron degeneration in vivo. Proc Natl Acad Sci U S A. 2011;108(43):17803–17808. DOI:https://doi.org/10.1073/pnas.1103141108.
- Lepore AC, Rauck B, Dejea C, et al. Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci. 2008;11(11):1294–1301. DOI:https://doi.org/10.1038/nn.2210.
- Bose JK, Huang CC, Shen CK. Regulation of autophagy by neuropathological protein TDP-43. J Biol Chem. 2011;286(52):44441–44448.
- Xia Q, Wang H, Hao Z, et al. TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion. Embo J. 2016;35(2):121–142. DOI:https://doi.org/10.15252/embj.201591998.
- Caccamo A, Shaw DM, Guarino F, et al. Reduced protein turnover mediates functional deficits in transgenic mice expressing the 25 kDa C-terminal fragment of TDP-43. Hum Mol Genet. 2015;24(16):4625–4635. DOI:https://doi.org/10.1093/hmg/ddv193.
- Caccamo A, Majumder S, Deng JJ, et al. Rapamycin rescues TDP-43 mislocalization and the associated low molecular mass neurofilament instability. J Biol Chem. 2009;284(40):27416–27424. DOI:https://doi.org/10.1074/jbc.M109.031278.
- Wang IF, Guo BS, Liu YC, et al. Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci U S A. 2012;109(37):15024–15029. DOI:https://doi.org/10.1073/pnas.1206362109.
- Jinwal UK, Abisambra JF, Zhang J, et al. Cdc37/Hsp90 protein complex disruption triggers an autophagic clearance cascade for TDP-43 protein. J Biol Chem. 2012;287(29):24814–24820. DOI:https://doi.org/10.1074/jbc.M112.367268.
- Crippa V, Carra S, Rusmini P, et al. A role of small heat shock protein B8 (HspB8) in the autophagic removal of misfolded proteins responsible for neurodegenerative diseases. Autophagy. 2010;6(7):958–960. DOI:https://doi.org/10.4161/auto.6.7.13042.
- Crippa V, D’Agostino VG, Cristofani R, et al. Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases. Sci Rep. 2016;6(1):22827. DOI:https://doi.org/10.1038/srep22827.
- Barmada SJ, Serio A, Arjun A, et al. Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol. 2014;10(8):677–685. DOI:https://doi.org/10.1038/nchembio.1563.
- Urushitani M, Sato T, Bamba H, et al. Synergistic effect between proteasome and autophagosome in the clearance of polyubiquitinated TDP-43. J Neurosci Res. 2010;88(4):784–797. DOI:https://doi.org/10.1002/jnr.22243.
- Wang X, Fan H, Ying Z, et al. Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin-proteasome system. Neurosci Lett. 2010;469(1):112–116. DOI:https://doi.org/10.1016/j.neulet.2009.11.055.
- Chen Y, Wang H, Ying Z, et al. Ibudilast enhances the clearance of SOD1 and TDP-43 aggregates through TFEB-mediated autophagy and lysosomal biogenesis: the new molecular mechanism of ibudilast and its implication for neuroprotective therapy. Biochem Biophys Res Commun. 2020;526(1):231–238. DOI:https://doi.org/10.1016/j.bbrc.2020.03.051.
- Natale G, Lenzi P, Lazzeri G, et al. Compartment-dependent mitochondrial alterations in experimental ALS, the effects of mitophagy and mitochondriogenesis. Front Cell Neurosci. 2015;9:434.
- Chen Y, Liu H, Guan Y, et al. The altered autophagy mediated by TFEB in animal and cell models of amyotrophic lateral sclerosis. Am J Transl Res. 2015;7(9):1574–1587.
- Guo X, Sun X, Hu D, et al. VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington’s disease. Nat Commun. 2016;7(1):12646. DOI:https://doi.org/10.1038/ncomms12646.
- Forloni G, Artuso V, La Vitola P, et al. Oligomeropathies and pathogenesis of Alzheimer and Parkinson’s diseases. Mov Disord. 2016;31(6):771–781. DOI:https://doi.org/10.1002/mds.26624.
- Corcia P, Couratier P, Blasco H, et al. Genetics of amyotrophic lateral sclerosis. Rev Neurol (Paris). 2017;173(5):254–262. DOI:https://doi.org/10.1016/j.neurol.2017.03.030.
- Redler RL, Dokholyan NV. The complex molecular biology of amyotrophic lateral sclerosis (ALS). Prog Mol Biol Transl Sci. 2012;107:215–262.
- Bucelli RC, Arhzaouy K, Pestronk A, et al. SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles. Neurology. 2015;85(8):665–674. DOI:https://doi.org/10.1212/WNL.0000000000001864.
- Manley S, Williams JA, Ding WX. Role of p62/SQSTM1 in liver physiology and pathogenesis. Exp Biol Med (Maywood). 2013;238(5):525–538.
- Lodish HF, Berk A, Zipursky SL, et al. Molecular Cell Biology. New York: W.H. Freeman; 2000. 1084.
- Maday S, Holzbaur EL. Compartment-Specific Regulation of Autophagy in Primary Neurons. J Neurosci. 2016;36(22):5933–5945.
- Horgusluoglu E, Nudelman K, Nho K, et al. Adult neurogenesis and neurodegenerative diseases: a systems biology perspective. Am J Med Genet B Neuropsychiatr Genet. 2017;174(1):93–112. DOI:https://doi.org/10.1002/ajmg.b.32429.
- Maday S, Wallace KE, Holzbaur EL. Autophagosomes initiate distally and mature during transport toward the cell soma in primary neurons. J Cell Biol. 2012;196(4):407–417.
- Maday S, Holzbaur EL. Autophagosome biogenesis in primary neurons follows an ordered and spatially regulated pathway. Dev Cell. 2014;30(1):71–85.
- Maday S, Holzbaur EL. Autophagosome assembly and cargo capture in the distal axon. Autophagy. 2012;8(5):858–860.
- Wang QJ, Ding Y, Kohtz DS, et al. Induction of autophagy in axonal dystrophy and degeneration. J Neurosci. 2006;26(31):8057–8068. DOI:https://doi.org/10.1523/JNEUROSCI.2261-06.2006.
- Komatsu M, Wang QJ, Holstein GR, et al. Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration. Proc Natl Acad Sci U S A. 2007;104(36):14489–14494. DOI:https://doi.org/10.1073/pnas.0701311104.
- Shen W, Ganetzky B. Autophagy promotes synapse development in Drosophila. J Cell Biol. 2009;187(1):71–79.
- Tang G, Gudsnuk K, Kuo SH, et al. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 2014;83(5):1131–1143. DOI:https://doi.org/10.1016/j.neuron.2014.07.040.
- Boland B, Kumar A, Lee S, et al. Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci. 2008;28(27):6926–6937. DOI:https://doi.org/10.1523/JNEUROSCI.0800-08.2008.
- Komatsu M, Waguri S, Chiba T, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature. 2006;441(7095):880–884. DOI:https://doi.org/10.1038/nature04723.
- Hara T, Nakamura K, Matsui M, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441(7095):885–889. DOI:https://doi.org/10.1038/nature04724.
- Stavoe AK, Gopal PP, Gubas A, et al. Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons. Elife. 2019;8:8.
- Mizushima N, Yamamoto A, Matsui M, et al. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004;15(3):1101–1111. DOI:https://doi.org/10.1091/mbc.e03-09-0704.
- Tsvetkov AS, Miller J, Arrasate M, et al. A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proc Natl Acad Sci U S A. 2010;107(39):16982–16987. DOI:https://doi.org/10.1073/pnas.1004498107.
- Roscic A, Baldo B, Crochemore C, et al. Induction of autophagy with catalytic mTOR inhibitors reduces huntingtin aggregates in a neuronal cell model. J Neurochem. 2011;119(2):398–407. DOI:https://doi.org/10.1111/j.1471-4159.2011.07435.x.
- Fox JH, Connor T, Chopra V, et al. The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington’s disease. Mol Neurodegener. 2010;5(1):26. DOI:https://doi.org/10.1186/1750-1326-5-26
- Arriola Apelo SI, Neuman JC, Baar EL, et al. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system. Aging Cell. 2016;15(1):28–38. DOI:https://doi.org/10.1111/acel.12405.
- Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274–293.
- Von Bartheld CS, Bahney J, Herculano-Houzel S. The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J Comp Neurol. 2016;524(18):3865–3895.
- Jessen KR. Glial cells. Int J Biochem Cell Biol. 2004;36(10):1861–1867.
- Von Bernhardi R, Eugenin-von Bernhardi J, Flores B, et al. Glial Cells and Integrity of the Nervous System. Adv Exp Med Biol. 2016;949:1–24.
- Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010;119(1):7–35.
- Yong VW, Yong FP, Olivier A, et al. Morphologic heterogeneity of human adult astrocytes in culture: correlation with HLA-DR expression. J Neurosci Res. 1990;27(4):678–688. DOI:https://doi.org/10.1002/jnr.490270428.
- Miller RH, Zhang H, Fok-Seang J. Glial cell heterogeneity in the mammalian spinal cord. Perspect Dev Neurobiol. 1994;2(3):225–231.
- Miller RH, Raff MC. Fibrous and protoplasmic astrocytes are biochemically and developmentally distinct. J Neurosci. 1984;4(2):585–592.
- Vaughn JE, Pease DC. Electron microscopy of classically stained astrocytes. J Comp Neurol. 1967;131(2):143–154.
- Nedelsky NB, Todd PK, Taylor JP. Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection. Biochim Biophys Acta. 2008;1782(12):691–699.
- Janen SB, Chaachouay H, Richter-Landsberg C. Autophagy is activated by proteasomal inhibition and involved in aggresome clearance in cultured astrocytes. Glia. 2010;58(14):1766–1774.
- Tang G, Yue Z, Talloczy Z, et al. Autophagy induced by Alexander disease-mutant GFAP accumulation is regulated by p38/MAPK and mTOR signaling pathways. Hum Mol Genet. 2008;17(11):1540–1555. DOI:https://doi.org/10.1093/hmg/ddn042.
- Pamenter ME, Perkins GA, McGinness AK, et al. Autophagy and apoptosis are differentially induced in neurons and astrocytes treated with an in vitro mimic of the ischemic penumbra. PLoS One. 2012;7(12):e51469. DOI:https://doi.org/10.1371/journal.pone.0051469.
- Motori E, Puyal J, Toni N, et al. Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab. 2013;18(6):844–859. DOI:https://doi.org/10.1016/j.cmet.2013.11.005.
- Kulkarni A, Dong A, Kulkarni VV, et al. Differential regulation of autophagy during metabolic stress in astrocytes and neurons. Autophagy. 2019;16(9):1651–1667.
- Lavieu G, Scarlatti F, Sala G, et al. Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation. J Biol Chem. 2006;281(13):8518–8527. DOI:https://doi.org/10.1074/jbc.M506182200.
- Lima S, Milstien S, Spiegel S. Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane Trafficking. J Biol Chem. 2017;292(8):3074–3088.
- Moruno Manchon JF, Uzor NE, Finkbeiner S, et al. SPHK1/sphingosine kinase 1-mediated autophagy differs between neurons and SH-SY5Y neuroblastoma cells. Autophagy. 2016;12(8):1418–1424. DOI:https://doi.org/10.1080/15548627.2016.1183082.
- Young MM, Takahashi Y, Fox TE, et al. Sphingosine Kinase 1 Cooperates with Autophagy to Maintain Endocytic Membrane Trafficking. Cell Rep. 2016;17(6):1532–1545. DOI:https://doi.org/10.1016/j.celrep.2016.10.019.
- Koistinaho M, Lin S, Wu X, et al. Apolipoprotein E promotes astrocyte colocalization and degradation of deposited amyloid-beta peptides. Nat Med. 2004;10(7):719–726. DOI:https://doi.org/10.1038/nm1058.
- Nielsen HM, Veerhuis R, Holmqvist B, et al. Binding and uptake of A beta1-42 by primary human astrocytes in vitro. Glia. 2009;57(9):978–988. DOI:https://doi.org/10.1002/glia.20822.
- Wyss-Coray T, Loike JD, Brionne TC, et al. Adult mouse astrocytes degrade amyloid-beta in vitro and in situ. Nat Med. 2003;9(4):453–457. DOI:https://doi.org/10.1038/nm838.
- Lee HJ, Suk JE, Patrick C, et al. Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem. 2010;285(12):9262–9272. DOI:https://doi.org/10.1074/jbc.M109.081125.
- Braidy N, Gai WP, Xu YH, et al. Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts. Transl Neurodegener. 2013;2(1):20. DOI:https://doi.org/10.1186/2047-9158-2-20.
- Lindstrom V, Gustafsson G, Sanders LH, et al. Extensive uptake of alpha-synuclein oligomers in astrocytes results in sustained intracellular deposits and mitochondrial damage. Mol Cell Neurosci. 2017;82:143–156.
- Chen LL, Wu JC, Wang LH, et al. Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes. Acta Pharmacol Sin. 2012;33(3):385–392. DOI:https://doi.org/10.1038/aps.2011.162.
- Bruijn LI, Becher MW, Lee MK, et al. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron. 1997;18(2):327–338. DOI:https://doi.org/10.1016/S0896-6273(00)80272-X.
- Tripathi P, Rodriguez-Muela N, Klim JR, et al. Reactive astrocytes promote ALS-like degeneration and intracellular protein aggregation in human motor neurons by disrupting autophagy through TGF-beta1. Stem Cell Reports. 2017;9(2):667–680. DOI:https://doi.org/10.1016/j.stemcr.2017.06.008.
- Hanamsagar R, Bilbo SD. Environment matters: microglia function and dysfunction in a changing world. Curr Opin Neurobiol. 2017;47:146–155.
- Schafer DP, Stevens B. Microglia Function in Central Nervous System Development and Plasticity. Cold Spring Harb Perspect Biol. 2015;7(10):a020545.
- Keren-Shaul H, Spinrad A, Weiner A, et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell. 2017;169(7):1276–1290.e17. DOI:https://doi.org/10.1016/j.cell.2017.05.018.
- Philips T, Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 2011;10(3):253–263.
- Gleichman AJ, Carmichael ST. Glia in neurodegeneration: drivers of disease or along for the ride?. Neurobiol Dis. 2020;142:104957.
- Haukedal H, Freude K. Implications of Microglia in amyotrophic lateral sclerosis and frontotemporal dementia. J Mol Biol. 2019;431(9):1818–1829.
- Thompson AG, Gray E, Thézénas ML, et al. Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis. Ann Neurol. 2018;83(2):258–268. DOI:https://doi.org/10.1002/ana.25143.
- Corcia P, Tauber C, Vercoullie J, et al. Molecular imaging of microglial activation in amyotrophic lateral sclerosis. PLoS One. 2012;7(12):e52941. DOI:https://doi.org/10.1371/journal.pone.0052941.
- Turner MR, Cagnin A, Turkheimer FE, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis. 2004;15(3):601–609. DOI:https://doi.org/10.1016/j.nbd.2003.12.012.
- Cady J, Koval ED, Benitez BA, et al. TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis. JAMA Neurol. 2014;71(4):449–453. DOI:https://doi.org/10.1001/jamaneurol.2013.6237.
- Colonna M. TREMs in the immune system and beyond. Nat Rev Immunol. 2003;3(6):445–453.
- Kleinberger G, Yamanishi Y, Suárez-Calvet M, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med. 2014;6(243):243ra86. DOI:https://doi.org/10.1126/scitranslmed.3009093.
- Plaza-Zabala A, Sierra-Torre V, Sierra A. Autophagy and Microglia: novel Partners in Neurodegeneration and Aging. Int J Mol Sci. 2017;18(3):3.
- Etchegaray JI, Elguero EJ, Tran JA, et al. Defective phagocytic corpse processing results in neurodegeneration and can be rescued by TORC1 activation. J Neurosci. 2016;36(11):3170–3183. DOI:https://doi.org/10.1523/JNEUROSCI.1912-15.2016.
- Sierra A, Abiega O, Shahraz A, et al. Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis. Front Cell Neurosci. 2013;7:6.
- Solé-Domènech S, Cruz DL, Capetillo-Zarate E, et al. The endocytic pathway in microglia during health, aging and Alzheimer’s disease. Ageing Res Rev. 2016;32:89–103. DOI:https://doi.org/10.1016/j.arr.2016.07.002
- Cho MH, Cho K, Kang HJ, et al. Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome. Autophagy. 2014;10(10):1761–1775. DOI:https://doi.org/10.4161/auto.29647.
- Lucin KM, O’Brien CE, Bieri G, et al. Microglial beclin 1 regulates retromer trafficking and phagocytosis and is impaired in Alzheimer’s disease. Neuron. 2013;79(5):873–886. DOI:https://doi.org/10.1016/j.neuron.2013.06.046.
- Haidet-phillips AM, Hester ME, Miranda CJ, et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol. 2011;29(9):824–828. DOI:https://doi.org/10.1038/nbt.1957.
- Henkel JS, Beers DR, Zhao W, et al. Microglia in ALS: the good, the bad, and the resting. J Neuroimmune Pharmacol. 2009;4(4):389–398. DOI:https://doi.org/10.1007/s11481-009-9171-5.
- Yamanaka K, Chun SJ, Boillee S, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci. 2008;11(3):251–253. DOI:https://doi.org/10.1038/nn2047.
- Beers DR, Henkel JS, Xiao Q, et al. Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis. Proc Natl Acad Sci USA. 2006;103(43):16021–16026.
- Brettschneider J, Toledo JB, Van Deerlin VM, et al. Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis. PLoS One. 2012;7(6):e39216. DOI:https://doi.org/10.1371/journal.pone.0039216.
- O’Rourke JG, Bogdanik L, Yáñez A, et al. C9orf72 is required for proper macrophage and microglial function in mice. Science. 2016;351(6279):1324–1329. DOI:https://doi.org/10.1126/science.aaf1064.
- McCauley ME, O’Rourke JG, Yáñez A, et al. C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature. 2020;585(7823):96–101. DOI:https://doi.org/10.1038/s41586-020-2625-x.
- Asai T, Tomita Y, Nakatsuka S, et al. VCP (p97) regulates NFkappaB signaling pathway, which is important for metastasis of osteosarcoma cell line. Jpn J Cancer Res. 2002;93(3):296–304. DOI:https://doi.org/10.1111/j.1349-7006.2002.tb02172.x.
- Duran A, Linares JF, Galvez AS, et al. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell. 2008;13(4):343–354. DOI:https://doi.org/10.1016/j.ccr.2008.02.001.
- Zhu G, Wu CJ, Zhao Y, et al. Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP. Curr Biol. 2007;17(16):1438–1443. DOI:https://doi.org/10.1016/j.cub.2007.07.041.
- Bankston AN, Forston MD, Howard RM, et al. Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination. Glia. 2019;67(9):1745–1759. DOI:https://doi.org/10.1002/glia.23646.
- Dello Russo C, Lisi L, Feinstein DL, et al. mTOR kinase, a key player in the regulation of glial functions: relevance for the therapy of multiple sclerosis. Glia. 2013;61(3):301–311. DOI:https://doi.org/10.1002/glia.22433.
- Figlia G, Gerber D, Suter U. Myelination and mTOR. Glia. 2018;66(4):693–707.
- Tyler WA, Gangoli N, Gokina P, et al. Activation of the mammalian target of rapamycin (mTOR) is essential for oligodendrocyte differentiation. J Neurosci. 2009;29(19):6367–6378. DOI:https://doi.org/10.1523/JNEUROSCI.0234-09.2009.
- Smith CM, Mayer JA, Duncan ID. Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant. J Neurosci. 2013;33(18):8088–8100.
- Saraswat Ohri S, Bankston AN, Mullins SA, et al. Blocking Autophagy in Oligodendrocytes Limits Functional Recovery after Spinal Cord Injury. J Neurosci. 2018;38(26):5900–5912. DOI:https://doi.org/10.1523/JNEUROSCI.0679-17.2018.
- Pukaß K, Goldbaum O, Richter-Landsberg C. Mitochondrial impairment and oxidative stress compromise autophagosomal degradation of α-synuclein in oligodendroglial cells. J Neurochem. 2015;135(1):194–205.
- Riedel M, Goldbaum O, Schwarz L, et al. 17-AAG induces cytoplasmic alpha-synuclein aggregate clearance by induction of autophagy. PLoS One. 2010;5(1):e8753. DOI:https://doi.org/10.1371/journal.pone.0008753.
- Cong Y, Wang C, Wang J, et al. NT-3 promotes oligodendrocyte proliferation and nerve function recovery after spinal cord injury by inhibiting autophagy pathway. J Surg Res. 2020;247:128–135.
- Liu S, Sarkar C, Dinizo M, et al. Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death. Cell Death Dis. 2015;6(1):e1582. DOI:https://doi.org/10.1038/cddis.2014.527.
- Kaji S, Maki T, Kinoshita H, et al. Pathological endogenous alpha-synuclein accumulation in oligodendrocyte precursor cells potentially induces inclusions in multiple system atrophy. Stem Cell Reports. 2018;10(2):356–365. DOI:https://doi.org/10.1016/j.stemcr.2017.12.001.
- Mackenzie IR, Ansorge O, Strong M, et al. Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation. Acta Neuropathol. 2011;122(1):87–98. DOI:https://doi.org/10.1007/s00401-011-0838-7.
- Mackenzie IR, Bigio EH, Ince PG, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol. 2007;61(5):427–434. DOI:https://doi.org/10.1002/ana.21147.
- Seilhean D, Cazeneuve C, Thuries V, et al. Accumulation of TDP-43 and alpha-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation. Acta Neuropathol. 2009;118(4):561–573. DOI:https://doi.org/10.1007/s00401-009-0545-9.
- Lee Y, Morrison BM, Li Y, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature. 2012;487(7408):443–448. DOI:https://doi.org/10.1038/nature11314.
- Jang SY, Shin YK, Park SY, et al. Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve. PLoS One. 2015;10(1):e0116624.
- Logan AM, Mammel AE, Robinson DC, et al. Schwann cell-specific deletion of the endosomal PI 3-kinase Vps34 leads to delayed radial sorting of axons, arrested myelination, and abnormal ErbB2-ErbB3 tyrosine kinase signaling. Glia. 2017;65(9):1452–1470. DOI:https://doi.org/10.1002/glia.23173.
- Zhang SJ, Li XX, Yu Y, et al. Schwann cell-specific PTEN and EGFR dysfunctions affect neuromuscular junction development by impairing Agrin signaling and autophagy. Biochem Biophys Res Commun. 2019;515(1):50–56. DOI:https://doi.org/10.1016/j.bbrc.2019.05.014.
- Brosius Lutz A, Chung WS, Sloan SA, et al. Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury. Proc Natl Acad Sci U S A. 2017;114(38):E8072–e8080. DOI:https://doi.org/10.1073/pnas.1710566114.
- Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, et al. Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves. J Cell Biol. 2015;210(1):153–168. DOI:https://doi.org/10.1083/jcb.201503019.
- Jang SY, Yoon BA, Shin YK, et al. Schwann cell dedifferentiation-associated demyelination leads to exocytotic myelin clearance in inflammatory segmental demyelination. Glia. 2017;65(11):1848–1862. DOI:https://doi.org/10.1002/glia.23200.
- Huang HC, Chen L, Zhang HX, et al. Autophagy promotes peripheral nerve regeneration and motor recovery following sciatic nerve crush injury in rats. J Mol Neurosci. 2016;58(4):416–423. DOI:https://doi.org/10.1007/s12031-015-0672-9.
- Marinelli S, Nazio F, Tinari A, et al. Schwann cell autophagy counteracts the onset and chronification of neuropathic pain. Pain. 2014;155(1):93–107. DOI:https://doi.org/10.1016/j.pain.2013.09.013.
- Hantke J, Carty L, Wagstaff LJ, et al. c-Jun activation in Schwann cells protects against loss of sensory axons in inherited neuropathy. Brain. 2014;137(11):2922–2937. DOI:https://doi.org/10.1093/brain/awu257.
- Hutton EJ, Carty L, Laura M, et al. c-Jun expression in human neuropathies: a pilot study. J Peripher Nerv Syst. 2011;16(4):295–303. DOI:https://doi.org/10.1111/j.1529-8027.2011.00360.x.
- Lee S, Bazick H, Chittoor-Vinod V, et al. Elevated peripheral myelin protein 22, reduced mitotic potential, and proteasome impairment in dermal fibroblasts from charcot-marie-tooth disease type 1A patients. Am J Pathol. 2018;188(3):728–738. DOI:https://doi.org/10.1016/j.ajpath.2017.10.021.
- Chow CY, Landers JE, Bergren SK, et al. Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am J Hum Genet. 2009;84(1):85–88. DOI:https://doi.org/10.1016/j.ajhg.2008.12.010.
- Fernandez AM, LeRoith D. Skeletal muscle. Adv Exp Med Biol. 2005;567:117–147.
- Wang X, Blagden C, Fan J, et al. Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle. Genes Dev. 2005;19(14):1715–1722. DOI:https://doi.org/10.1101/gad.1318305.
- Mammucari C, Milan G, Romanello V, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6(6):458–471. DOI:https://doi.org/10.1016/j.cmet.2007.11.001.
- Campos JC, Baehr LM, Ferreira ND, et al. beta2 -adrenoceptor activation improves skeletal muscle autophagy in neurogenic myopathy. Faseb J. 2020;34(4):5628–5641. DOI:https://doi.org/10.1096/fj.201902305R.
- Nichenko AS, Southern WM, Atuan M, et al. Mitochondrial maintenance via autophagy contributes to functional skeletal muscle regeneration and remodeling. Am J Physiol Cell Physiol. 2016;311(2):C190–200. DOI:https://doi.org/10.1152/ajpcell.00066.2016.
- Saera-Vila A, Kish PE, Louie KW, et al. Autophagy regulates cytoplasmic remodeling during cell reprogramming in a zebrafish model of muscle regeneration. Autophagy. 2016;12(10):1864–1875. DOI:https://doi.org/10.1080/15548627.2016.1207015.
- Masiero E, Agatea L, Mammucari C, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009;10(6):507–515. DOI:https://doi.org/10.1016/j.cmet.2009.10.008.
- Raben N, Hill V, Shea L, et al. Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. Hum Mol Genet. 2008;17(24):3897–3908. DOI:https://doi.org/10.1093/hmg/ddn292.
- Dobrowolny G, Aucello M, Rizzuto E, et al. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab. 2008;8(5):425–436. DOI:https://doi.org/10.1016/j.cmet.2008.09.002.
- Bibee KP, Cheng YJ, Ching JK, et al. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. Faseb J. 2014;28(5):2047–2061. DOI:https://doi.org/10.1096/fj.13-237388.
- Pauly M, Daussin F, Burelle Y, et al. AMPK activation stimulates autophagy and ameliorates muscular dystrophy in the mdx mouse diaphragm. Am J Pathol. 2012;181(2):583–592. DOI:https://doi.org/10.1016/j.ajpath.2012.04.004.
- Salminen A, Vihko V. Autophagic response to strenuous exercise in mouse skeletal muscle fibers. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(1):97–106.
- Fry CS, Drummond MJ, Glynn EL, et al. Skeletal muscle autophagy and protein breakdown following resistance exercise are similar in younger and older adults. J Gerontol A Biol Sci Med Sci. 2013;68(5):599–607. DOI:https://doi.org/10.1093/gerona/gls209.
- Moller AB, Vendelbo MH, Christensen B, et al. Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle. J Appl Physiol. 1985;118(8):971–979. DOI:https://doi.org/10.1152/japplphysiol.01116.2014.
- He C, Bassik MC, Moresi V, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012;481(7382):511–515. DOI:https://doi.org/10.1038/nature10758.
- Jamart C, Francaux M, Millet GY, et al. Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running. J Appl Physiol (1985). 2012;112(9):1529–1537. DOI:https://doi.org/10.1152/japplphysiol.00952.2011
- Jamart C, Benoit N, Raymackers JM, et al. Autophagy-related and autophagy-regulatory genes are induced in human muscle after ultraendurance exercise. Eur J Appl Physiol. 2012;112(8):3173–3177. DOI:https://doi.org/10.1007/s00421-011-2287-3.
- Vainshtein A, Tryon LD, Pauly M, et al. Role of PGC-1alpha during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol Cell Physiol. 2015;308(9):C710–9.
- Fan J, Kou X, Jia S, et al. Autophagy as a Potential Target for Sarcopenia. J Cell Physiol. 2016;231(7):1450–1459. DOI:https://doi.org/10.1002/jcp.25260.
- Demontis F, Perrimon N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010;143(5):813–825.
- Kim YA, Kim YS, Oh SL, et al. Autophagic response to exercise training in skeletal muscle with age. J Physiol Biochem. 2013;69(4):697–705. DOI:https://doi.org/10.1007/s13105-013-0246-7.
- Sebastian D, Sorianello E, Segales J, et al. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. Embo J. 2016;35(15):1677–1693. DOI:https://doi.org/10.15252/embj.201593084.
- Halling JF, Ringholm S, Olesen J, et al. Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1alpha dependent manner. Exp Gerontol. 2017;96:1–6.
- Russ DW, Boyd IM, McCoy KM, et al. Muscle-specificity of age-related changes in markers of autophagy and sphingolipid metabolism. Biogerontology. 2015;16(6):747–759. DOI:https://doi.org/10.1007/s10522-015-9598-4.
- Wenz T, Rossi SG, Rotundo RL, et al. Increased muscle PGC-1alpha expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci U S A. 2009;106(48):20405–20410. DOI:https://doi.org/10.1073/pnas.0911570106.
- O’Leary MF, Vainshtein A, Iqbal S, et al. Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle. Am J Physiol Cell Physiol. 2013;304(5):C422–30. DOI:https://doi.org/10.1152/ajpcell.00240.2012.
- Carter HN, Kim Y, Erlich AT, et al. Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity. J Physiol. 2018;596(16):3567–3584. DOI:https://doi.org/10.1113/JP275998.
- Mandrioli J, D’Amico R, Zucchi E, et al. Rapamycin treatment for amyotrophic lateral sclerosis: protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial). Medicine (Baltimore). 2018;97(24):e11119. DOI:https://doi.org/10.1097/MD.0000000000011119.
- Li M, Zhou Y, Chen C, et al. Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis. Orphanet J Rare Dis. 2019;14(1):39. DOI:https://doi.org/10.1186/s13023-019-1012-x.
- Lutz M, Mielke S. New perspectives on the use of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation and graft-versus-host disease. Br J Clin Pharmacol. 2016;82(5):1171–1179.
- Nguyen LS, Vautier M, Allenbach Y, et al. Sirolimus and mTOR Inhibitors: a Review of Side Effects and Specific Management in Solid Organ Transplantation. Drug Saf. 2019;42(7):813–825. DOI:https://doi.org/10.1007/s40264-019-00810-9.
- Sofroniadou S, Goldsmith D. Mammalian target of rapamycin (mTOR) inhibitors: potential uses and a review of haematological adverse effects. Drug Saf. 2011;34(2):97–115.
- Pallet N, Legendre C. Adverse events associated with mTOR inhibitors. Expert Opin Drug Saf. 2013;12(2):177–186.
- Kahan BD, Napoli KL, Kelly PA, et al. Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity. Clin Transplant. 2000;14(2):97–109. DOI:https://doi.org/10.1034/j.1399-0012.2000.140201.x.
- Fornai F, Longone P, Cafaro L, et al. Lithium delays progression of amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2008;105(6):2052–2057. DOI:https://doi.org/10.1073/pnas.0708022105.
- Fornai F, Longone P, Ferrucci M, et al. Autophagy and amyotrophic lateral sclerosis: the multiple roles of lithium. Autophagy. 2008;4(4):527–530. DOI:https://doi.org/10.4161/auto.5923.
- Aggarwal SP, Zinman L, Simpson E, et al. Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010;9(5):481–488. DOI:https://doi.org/10.1016/S1474-4422(10)70068-5.
- Chio A, Borghero G, Calvo A, et al. Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial. Neurology. 2010;75(7):619–625. DOI:https://doi.org/10.1212/WNL.0b013e3181ed9e7c.
- Miller RG, Moore DH, Forshew DA, et al. Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: examining a more efficient trial design. Neurology. 2011;77(10):973–979. DOI:https://doi.org/10.1212/WNL.0b013e31822dc7a5.
- Morrison KE, Dhariwal S, Hornabrook R, et al. Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013;12(4):339–345.
- Verstraete E, Veldink JH, Huisman MH, et al. Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial. J Neurol Neurosurg Psychiatry. 2012;83(5):557–564. DOI:https://doi.org/10.1136/jnnp-2011-302021.
- Kanazawa T, Taneike I, Akaishi R, et al. Amino acids and insulin control autophagic proteolysis through different signaling pathways in relation to mTOR in isolated rat hepatocytes. J Biol Chem. 2004;279(9):8452–8459. DOI:https://doi.org/10.1074/jbc.M306337200.
- Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280–293.
- Wang RC, Wei Y, An Z, et al. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science. 2012;338(6109):956–959. DOI:https://doi.org/10.1126/science.1225967.
- Wei Y, Pattingre S, Sinha S, et al. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008;30(6):678–688. DOI:https://doi.org/10.1016/j.molcel.2008.06.001.
- Shoji-Kawata S, Sumpter R, Leveno M, et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494(7436):201–206. DOI:https://doi.org/10.1038/nature11866.
- Wengrod J, Martin L, Wang D, et al. Inhibition of nonsense-mediated RNA decay activates autophagy. Mol Cell Biol. 2013;33(11):2128–2135. DOI:https://doi.org/10.1128/MCB.00174-13.
- Daub A, Sharma P, Finkbeiner S. High-content screening of primary neurons: ready for prime time. Curr Opin Neurobiol. 2009;19(5):537–543.
- Engle SJ, Vincent F. Small molecule screening in human induced pluripotent stem cell-derived terminal cell types. J Biol Chem. 2014;289(8):4562–4570.
- Sarkar S, Perlstein EO, Imarisio S, et al. Small molecules enhance autophagy and reduce toxicity in Huntington’s disease models. Nat Chem Biol. 2007;3(6):331–338. DOI:https://doi.org/10.1038/nchembio883.