Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration

References

• Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12:1–222.
   PubMed Web of Science ®Google Scholar
• Galluzzi L, Bravo-San Pedro JM, Levine B, et al. Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles. Nat Rev Drug Discov. 2017;16:487–511.
   PubMed Web of Science ®Google Scholar
• Jackson MP, Hewitt EW. Cellular proteostasis: degradation of misfolded proteins by lysosomes. Essays Biochem. 2016;60:173–180.
   PubMed Web of Science ®Google Scholar
• Haidar M, Timmerman V. Autophagy as an emerging common pathomechanism in inherited peripheral neuropathies. Front Mol Neurosci. 2017;10:143.
   PubMed Web of Science ®Google Scholar
• Lumkwana D, Du Toit A, Kinnear C, et al. Autophagic flux control in neurodegeneration: progress and precision targeting-Where do we stand? Progr Neurobiol. 2017;153:64–85.
   PubMed Web of Science ®Google Scholar
• Menzies FM, Fleming A, Caricasole A, et al. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron. 2017;93:1015–1034.
   PubMed Web of Science ®Google Scholar
• Sarkar S, Rubinsztein DC. Huntington’s disease: degradation of mutant huntingtin by autophagy. FEBS J. 2008;275:4263–4270.
   PubMed Web of Science ®Google Scholar
• Sarkar S, Rubinsztein DC. Small molecule enhancers of autophagy for neurodegenerative diseases. Mol Biosyst. 2008;4:895–901.
   PubMed Web of Science ®Google Scholar
• Sarkar S, Davies JE, Huang Z, et al. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem. 2007;282:5641–5652.
   PubMed Web of Science ®Google Scholar
• Rusmini P, Crippa V, Giorgetti E, et al. Clearance of the mutant androgen receptor in motoneuronal models of spinal and bulbar muscular atrophy. Neurobiol Aging. 2013;34:2585–2603.
   PubMed Web of Science ®Google Scholar
• Lan DM, Liu FT, Zhao J, et al. Effect of trehalose on PC12 cells overexpressing wild-type or A53T mutant alpha-synuclein. Neurochem Res. 2012;37:2025–2032.
   PubMed Web of Science ®Google Scholar
• 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;469:112–116.
   PubMed Web of Science ®Google Scholar
• Aguib Y, Heiseke A, Gilch S, et al. Autophagy induction by trehalose counteracts cellular prion infection. Autophagy. 2009;5:361–369.
   PubMed Web of Science ®Google Scholar
• Casarejos MJ, Perucho J, Lopez-Sendon JL, et al. Trehalose improves human fibroblast deficits in a new CHIP-mutation related ataxia. PloS one. 2014;9:e106931.
   PubMed Web of Science ®Google Scholar
• He Q, Koprich JB, Wang Y, et al. Treatment with trehalose prevents behavioral and neurochemical deficits produced in an AAV alpha-synuclein rat model of Parkinson’s disease. Mol Neurobiol. 2016;53:2258–2268.
   PubMed Web of Science ®Google Scholar
• Zhang X, Chen S, Song L, et al. MTOR-independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of amyotrophic lateral sclerosis. Autophagy. 2014;10:588–602.
   PubMed Web of Science ®Google Scholar
• Sarkar S, Chigurupati S, Raymick J, et al. Neuroprotective effect of the chemical chaperone, trehalose in a chronic MPTP-induced Parkinson’s disease mouse model. Neurotoxicology. 2014;44:250–262.
   PubMed Web of Science ®Google Scholar
• Du J, Liang Y, Xu F, et al. Trehalose rescues Alzheimer’s disease phenotypes in APP/PS1 transgenic mice. J Pharm Pharmacol. 2013;65:1753–1756.
   PubMed Web of Science ®Google Scholar
• Castillo K, Nassif M, Valenzuela V, et al. Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy. 2013;9:1308–1320.
   PubMed Web of Science ®Google Scholar
• Schaeffer V, Lavenir I, Ozcelik S, et al. Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain. 2012;135:2169–2177.
   PubMed Web of Science ®Google Scholar
• Schaeffer V, Goedert M. Stimulation of autophagy is neuroprotective in a mouse model of human tauopathy. Autophagy. 2012;8:1686–1687.
   PubMed Web of Science ®Google Scholar
• Perucho J, Casarejos MJ, Gomez A, et al. Trehalose protects from aggravation of amyloid pathology induced by isoflurane anesthesia in APP(swe) mutant mice. Curr Alzheimer Res. 2012;9:334–343.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Navarro JA, Rodriguez L, Casarejos MJ, et al. Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activation. Neurobiol Dis. 2010;39:423–438.
   PubMed Web of Science ®Google Scholar
• Davies JE, Sarkar S, Rubinsztein DC. Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy. Hum Mol Genet. 2006;15:23–31.
   PubMed Web of Science ®Google Scholar
• Tanaka M, Machida Y, Niu S, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004;10:148–154.
   PubMed Web of Science ®Google Scholar
• Debnath K, Pradhan N, Singh BK, et al. Poly(trehalose) nanoparticle prevents amyloid aggregation and suppress polyglutamine aggregation in huntington’s disease model mouse. ACS Appl Mater Inter. 2017;9:24126–24139.
   PubMed Web of Science ®Google Scholar
• Giorgetti E, Rusmini P, Crippa V, et al. Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy. Hum Mol Genet. 2015;24:64–75.
   PubMed Web of Science ®Google Scholar
• Chen X, Li M, Li L, et al. Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. Sci Rep. 2016;6:28423.
   PubMed Web of Science ®Google Scholar
• Montie HL, Merry DE. Autophagy and access: understanding the role of androgen receptor subcellular localization in SBMA. Autophagy. 2009;5:1194–1197.
   PubMed Web of Science ®Google Scholar
• Palmieri M, Pal R, Nelvagal HR, et al. mTORC1-independent TFEB activation via Akt inhibition promotes cellular clearance in neurodegenerative storage diseases. Nat Commun. 2017;8:14338.
   PubMed Web of Science ®Google Scholar
• Mardones P, Rubinsztein DC, Hetz C. Mystery solved: trehalose kickstarts autophagy by blocking glucose transport. Sci Signal. 2016;9:fs2.
   PubMed Web of Science ®Google Scholar
• DeBosch BJ, Heitmeier MR, Mayer AL, et al. Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis. Sci Signal. 2016;9:ra21.
   PubMed Web of Science ®Google Scholar
• Mayer AL, Higgins CB, Heitmeier MR, et al. SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy. Sci Rep. 2016;6:38586.
   PubMed Web of Science ®Google Scholar
• Dehay B, Bove J, Rodriguez-Muela N, et al. Pathogenic lysosomal depletion in Parkinson’s disease. J Neurosci. 2010;30:12535–12544.
   PubMed Web of Science ®Google Scholar
• Sardiello M, Palmieri M, di Ronza A, et al. A gene network regulating lysosomal biogenesis and function. Science. 2009;325:473–477.
   PubMed Web of Science ®Google Scholar
• Medina DL, Fraldi A, Bouche V, et al. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev Cell. 2011;21:421–430.
   PubMed Web of Science ®Google Scholar
• Palmieri M, Impey S, Kang H, et al. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum Mol Genet. 2011;20:3852–3866.
   PubMed Web of Science ®Google Scholar
• Settembre C, Ballabio A. TFEB regulates autophagy: an integrated coordination of cellular degradation and recycling processes. Autophagy. 2011;7:1379–1381.
   PubMed Web of Science ®Google Scholar
• Medina DL, Ballabio A. Lysosomal calcium regulates autophagy. Autophagy. 2015;11:970–971.
   PubMed Web of Science ®Google Scholar
• Medina DL, Di Paola S, Peluso I, et al. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat Cell Biol. 2015;17:288–299.
   PubMed Web of Science ®Google Scholar
• Valero T. Mitochondrial biogenesis: pharmacological approaches. Cur Pharm Design. 2014;20:5507–5509.
   PubMed Web of Science ®Google Scholar
• Sanchis-Gomar F, Garcia-Gimenez JL, Gomez-Cabrera MC, et al. Mitochondrial biogenesis in health and disease. Molecular and Therapeutic Approaches. Cur Pharm Design. 2014;20:5619–5633.
   PubMed Web of Science ®Google Scholar
• Dorn GW II, Vega RB, Kelly DP. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Gene Dev. 2015;29:1981–1991.
   PubMed Web of Science ®Google Scholar
• Chauhan S, Goodwin JG, Chauhan S, et al. ZKSCAN3 is a master transcriptional repressor of autophagy. Molecular Cell. 2013;50:16–28.
   PubMed Web of Science ®Google Scholar
• Arndt V, Dick N, Tawo R, et al. Chaperone-assisted selective autophagy is essential for muscle maintenance. Curr Biol. 2010;20:143–148.
   PubMed Web of Science ®Google Scholar
• Kettern N, Rogon C, Limmer A, et al. The Hsc/Hsp70 co-chaperone network controls antigen aggregation and presentation during maturation of professional antigen presenting cells. PloS one. 2011;6:e16398.
   PubMed Web of Science ®Google Scholar
• Ulbricht A, Gehlert S, Leciejewski B, et al. Induction and adaptation of chaperone-assisted selective autophagy CASA in response to resistance exercise in human skeletal muscle. Autophagy. 2015;11:538–546.
   PubMed Web of Science ®Google Scholar
• Ghaoui R, Palmio J, Brewer J, et al. Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy. Neurology. 2016;86:391–398.
   PubMed Web of Science ®Google Scholar
• Cristofani R, Crippa V, Rusmini P, et al. Inhibition of retrograde transport modulates misfolded protein accumulation and clearance in motoneuron diseases. Autophagy. 2017;13:1280–1303.
   PubMed Web of Science ®Google Scholar
• Rusmini P, Crippa V, Cristofani R, et al. The role of the protein quality control system in SBMA. J Mol Neurosci. 2016;58:348–364.
   PubMed Web of Science ®Google Scholar
• Rusmini P, Cristofani R, Galbiati M, et al. The role of the Heat Shock Protein B8 (HSPB8) in motoneuron diseases. Front Mol Neurosci. 2017;10:176.
   PubMed Web of Science ®Google Scholar
• Behl C. Breaking BAG: the co-chaperone BAG3 in health and disease. Trends Pharmacol Sci. 2016;37:672–688.
   PubMed Web of Science ®Google Scholar
• Gamerdinger M, Kaya AM, Wolfrum U, et al. BAG3 mediates chaperone-based aggresome-targeting and selective autophagy ofmisfolded proteins. EMBO Rep. 2011;12:149–156.
   PubMed Web of Science ®Google Scholar
• Gamerdinger M, Carra S, Behl C. Emerging roles of molecular chaperones and co-chaperones in selective autophagy: focus on BAG proteins. J Mol Med. 2011;89:1175–1182.
   PubMed Web of Science ®Google Scholar
• Simeoni S, Mancini MA, Stenoien DL, et al. Motoneuronal cell death is not correlated with aggregate formation of androgen receptors containing an elongated polyglutamine tract. Hum Mol Genet. 2000;9:133–144.
   PubMed Web of Science ®Google Scholar
• Piccioni F, Pinton P, Simeoni S, et al. Androgen receptor with elongated polyglutamine tract forms aggregates that alter axonal trafficking and mitochondrial distribution in motor neuronal processes. FASEB J. 2002;16:1418–1420.
   PubMed Web of Science ®Google Scholar
• Poletti A. The polyglutamine tract of androgen receptor: from functions to dysfunctions in motor neurons. Front Neuroendocrinol. 2004;25:1–26.
   PubMed Web of Science ®Google Scholar
• Rusmini P, Sau D, Crippa V, et al. Aggregation and proteasome: the case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy. Neurobiol Aging. 2007;28:1099–1111.
   PubMed Web of Science ®Google Scholar
• Rusmini P, Bolzoni E, Crippa V, et al. Proteasomal and autophagic degradative activities in spinal and bulbar muscular atrophy. Neurobiol Dis. 2010;40:361–369.
   PubMed Web of Science ®Google Scholar
• Rusmini P, Simonini F, Crippa V, et al. 17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy. Neurobiol Dis. 2011;41:83–95.
   PubMed Web of Science ®Google Scholar
• Cristofani R, Crippa V, Vezzoli G, et al. The small heat shock protein B8 (HSPB8) efficiently removes aggregating species of dipeptides produced in C9ORF72-related neurodegenerative diseases. Cell Stress Chaperon. 2017. DOI:10.1007/s12192-017-0806-9.
   PubMed Web of Science ®Google Scholar
• Crippa V, Sau D, Rusmini P, et al. The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS). Hum Mol Genet. 2010;19:3440–3456.
   PubMed Web of Science ®Google Scholar
• Crippa V, Cicardi ME, Ramesh N, et al. The chaperone HSPB8 reduces the accumulation of truncated TDP-43 species in cells and protects against TDP-43-mediated toxicity. Hum Mol Genet. 2016;25:3908–3924.
   PubMed Web of Science ®Google Scholar
• Cascella R, Fani G, Capitini C, et al. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy. FASEB J. 2017. DOI:10.1096/fj.201700292RR.
   PubMed Web of Science ®Google Scholar
• Zydowsky LD, Etzkorn FA, Chang HY, et al. Active site mutants of human cyclophilin A separate peptidyl-prolyl isomerase activity from cyclosporin A binding and calcineurin inhibition. Protein Sci. 1992;1:1092–1099.
   PubMed Web of Science ®Google Scholar
• Aits S, Kricker J, Liu B, et al. Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay. Autophagy. 2015;11:1408–1424.
   PubMed Web of Science ®Google Scholar
• Paz I, Sachse M, Dupont N, et al. Galectin-3, a marker for vacuole lysis by invasive pathogens. Cell Microbiol. 2010;12:530–544.
   PubMed Web of Science ®Google Scholar
• Maejima I, Takahashi A, Omori H, et al. Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. Embo J. 2013;32:2336–2347.
   PubMed Web of Science ®Google Scholar
• Gudmand-Hoyer E, Fenger HJ, Skovbjerg H, et al. Trehalase deficiency in Greenland. Scand J Gastroenterol. 1988;23:775–778.
   PubMed Web of Science ®Google Scholar
• Lin CH, Wu YR, Yang JM, et al. Novel lactulose and melibiose targeting autophagy to reduce PolyQ aggregation in cell models of spinocerebellar ataxia 3. CNS Neurol Disord-DR. 2016;15:351–359.
   Google Scholar
• Lee GC, Lin CH, Tao YC, et al. The potential of lactulose and melibiose, two novel trehalase-indigestible and autophagy-inducing disaccharides, for polyQ-mediated neurodegenerative disease treatment. Neurotoxicology. 2015;48:120–130.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Muela N, Hernandez-Pinto AM, Serrano-Puebla A, et al. Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa. Cell Death Differ. 2015;22:476–487.
   PubMed Web of Science ®Google Scholar
• Chauhan S, Kumar S, Jain A, et al. TRIMs and galectins globally cooperate and TRIM16 and galectin-3 co-direct autophagy in endomembrane damage homeostasis. Dev Cell. 2016;39:13–27.
   PubMed Web of Science ®Google Scholar
• Kumar S, Chauhan S, Jain A, et al. Galectins and TRIMs directly interact and orchestrate autophagic response to endomembrane damage. Autophagy. 2017:1–2. DOI:10.1080/15548627.2017.1307487.
   Web of Science ®Google Scholar
• Anding AL, Baehrecke EH. Cleaning house: selective autophagy of organelles. Dev Cell. 2017;41:10–22.
   PubMed Web of Science ®Google Scholar
• Kawabata T, Yoshimori T. Beyond starvation: an update on the autophagic machinery and its functions. J Mol Cell Cardiol. 2016;95:2–10.
   PubMed Web of Science ®Google Scholar
• Settembre C, Medina DL. TFEB and the CLEAR network. Methods Cell Biol. 2015;126:45–62.
   PubMed Web of Science ®Google Scholar
• Zhang YJ, Xu YF, Cook C, et al. Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc Natl Acad Sci U.S.A. 2009;106:7607–7612.
   PubMed Web of Science ®Google Scholar
• 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;6:958–960.
   PubMed Web of Science ®Google Scholar
• Cashman NR, Durham HD, Blusztajn JK, et al. Neuroblastoma x spinal cord (NSC) hybrid cell lines resemble developing motor neurons. Devel Dyn. 1992;194:209–221.
   PubMed Web of Science ®Google Scholar
• Durham HD, Dahrouge S, Cashman NR. Evaluation of the spinal cord neuron X neuroblastoma hybrid cell line NSC-34 as a model for neurotoxicity testing. Neurotoxicol. 1992;14:387–395.
   Web of Science ®Google Scholar
• Reinhardt P, Glatza M, Hemmer K, et al. Derivation and expansion using only small molecules of human neural progenitors for neurodegenerative disease modeling. PloS one. 2013;8:e59252.
   PubMed Web of Science ®Google Scholar
• Thellung S, Scoti B, Corsaro A, et al. Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death. Cell Death Dis. 2018;9:166.
   PubMed Web of Science ®Google Scholar