1,423
Views
19
CrossRef citations to date
0
Altmetric
Review

Organoid and pluripotent stem cells in Parkinson’s disease modeling: an expert view on their value to drug discovery

, &
Pages 427-441 | Received 14 Aug 2019, Accepted 09 Dec 2019, Published online: 03 Jan 2020

References

  • Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663–676. PubMed PMID: 16904174.
  • Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858):1917–1920. .
  • Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without myc from mouse and human fibroblasts. Nat Biotechnol. 2008 Jan;26(1):101–106. PubMed PMID: 18059259.
  • Gu H, Huang X, Xu J, et al. Optimizing the method for generation of integration-free induced pluripotent stem cells from human peripheral blood. Stem Cell Res Ther. 2018 Jun 15;9(1):163. PubMed PMID: 29907164; PubMed Central PMCID: PMCPMC6002980.
  • Qu X, Liu T, Song K, et al. Induced pluripotent stem cells generated from human adipose-derived stem cells using a non-viral polycistronic plasmid in feeder-free conditions. PLoS One. 2012;7(10):e48161. PubMed PMID: 23110200; PubMed Central PMCID: PMCPMC3482207.
  • Takenaka C, Nishishita N, Takada N, et al. Effective generation of iPS cells from CD34+ cord blood cells by inhibition of p53. Exp Hematol. 2010 Feb;38(2):154–162. PubMed PMID: 19922768.
  • Wiedemann A, Hemmer K, Bernemann I, et al. Induced pluripotent stem cells generated from adult bone marrow-derived cells of the nonhuman primate (Callithrix jacchus) using a novel quad-cistronic and excisable lentiviral vector. Cell Reprogram. 2012 Dec;14(6):485–496. PubMed PMID: 23194452.
  • Urbach A, Schuldiner M, Benvenisty N. Modeling for lesch-nyhan disease by gene targeting in human embryonic stem cells. Stem Cells. 2004;22(4):635–641. . PubMed PMID: 15277709.
  • Robertson JA. Human embryonic stem cell research: ethical and legal issues. Nat Rev Genet. 2001 Jan 01;2(1):74–78. .
  • Barker RA, de Beaufort I. Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain. Prog Neurobiol. 2013 Nov;110:63–73. PubMed PMID: 23665410.
  • Arthur KC, Calvo A, Price TR, et al. Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun. 2016 Aug;11(7):12408. PubMed PMID: 27510634; PubMed Central PMCID: PMCPMC4987527.
  • Burbulla LF, Song P, Mazzulli JR, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease. Science. 2017 Sep 22;357(6357):1255–1261. PubMed PMID: 28882997.
  • Gitler AD, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Dis Model Mech. 2017 May 1;10(5):499–502. PubMed PMID: 28468935; PubMed Central PMCID: PMCPMC5451177.
  • Chambers SM, Fasano CA, Papapetrou EP, et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009 Mar;27(3):275–280. PubMed PMID: 19252484; PubMed Central PMCID: PMCPMC2756723.
  • Abud EM, Ramirez RN, Martinez ES, et al. iPSC-derived human microglia-like cells to study neurological diseases. Neuron. 2017 Apr 19;94(2):278–293 e9. PubMed PMID: 28426964; PubMed Central PMCID: PMCPMC5482419.
  • Emdad L, D’Souza SL, Kothari HP, et al. Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes. Stem Cells Dev. 2012 Feb 10;21(3):404–410. PubMed PMID: 21631388.
  • Hu Y, Qu ZY, Cao SY, et al. Directed differentiation of basal forebrain cholinergic neurons from human pluripotent stem cells. J Neurosci Methods. 2016 Jun;15(266):42–49. PubMed PMID: 27036311.
  • Kirkeby A, Grealish S, Wolf DA, et al. Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Rep. 2012 Jun 28;1(6):703–714. PubMed PMID: 22813745.
  • Kirkeby A, Nolbrant S, Tiklova K, et al. Predictive markers guide differentiation to improve graft outcome in clinical translation of hESC-based therapy for Parkinson’s disease. Cell Stem Cell. 2017 Jan 5;20(1):135–148. PubMed PMID: 28094017; PubMed Central PMCID: PMCPMC5222722.
  • Kriks S, Shim JW, Piao J, et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature. 2011 Nov 6;480(7378):547–551. PubMed PMID: 22056989; PubMed Central PMCID: PMCPMC3245796.
  • Little D, Ketteler R, Gissen P, et al. Using stem cell–derived neurons in drug screening for neurological diseases. Neurobiol Aging. 2019;78:130–141.
  • Lu J, Zhong X, Liu H, et al. Generation of serotonin neurons from human pluripotent stem cells. Nat Biotechnol. 2016 Jan;34(1):89–94. PubMed PMID: 26655496; PubMed Central PMCID: PMCPMC4711820.
  • Maroof AM, Keros S, Tyson JA, et al. Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells. Cell Stem Cell. 2013 May 2;12(5):559–572. PubMed PMID: 23642365; PubMed Central PMCID: PMCPMC3681523.
  • Merkle FT, Maroof A, Wataya T, et al. Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Development. 2015 Feb 15;142(4):633–643. PubMed PMID: 25670790; PubMed Central PMCID: PMCPMC4325380.
  • Nicholas CR, Chen J, Tang Y, et al. Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell. 2013 May 2;12(5):573–586. PubMed PMID: 23642366; PubMed Central PMCID: PMCPMC3699205.
  • Nistor GI, Totoiu MO, Haque N, et al. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia. 2005 Feb;49(3):385–396. PubMed PMID: 15538751.
  • Nizzardo M, Simone C, Falcone M, et al. Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells. Cell Mol Life Sci. 2010 Nov;67(22):3837–3847. PubMed PMID: 20668908.
  • Shi Y, Kirwan P, Livesey FJ. Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks. Nat Protoc. 2012 Oct;7(10):1836–1846. PubMed PMID: 22976355.
  • Wang S, Wang B, Pan N, et al. Differentiation of human induced pluripotent stem cells to mature functional Purkinje neurons. Sci Rep. 2015 Mar;18(5):9232. PubMed PMID: 25782665; PubMed Central PMCID: PMCPMC4363833.
  • Yang N, Chanda S, Marro S, et al. Generation of pure GABAergic neurons by transcription factor programming. Nat Methods. 2017 Jun;14(6):621–628. PubMed PMID: 28504679; PubMed Central PMCID: PMCPMC5567689.
  • Yu Diana X, Di Giorgio Francesco P, Yao J, et al. Modeling hippocampal neurogenesis using human pluripotent stem cells. Stem Cell Reports. 2014 Mar 11;2(3):295–310. .
  • Gunhanlar N, Shpak G, van der Kroeg M, et al. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Mol Psychiatry. 2018 May;23(5):1336–1344. PubMed PMID: 28416807; PubMed Central PMCID: PMCPMC5984104.
  • Bardy C, van den Hurk M, Eames T, et al. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2725–34. PubMed PMID: 25870293; PubMed Central PMCID: PMCPMC4443325.
  • Kikuchi T, Morizane A, Doi D, et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature. 2017 Aug 30;548(7669):592–596. PubMed PMID: 28858313.
  • Garcia-Leon JA, Vitorica J, Gutierrez A. Use of human pluripotent stem cell-derived cells for neurodegenerative disease modeling and drug screening platform. Future Med Chem. 2019 Jun;11(11):1305–1322. PubMed PMID: 31161803.
  • Nakano T, Ando S, Takata N, et al. Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell. 2012 Jun 14;10(6):771–785. PubMed PMID: 22704518.
  • Velasco S, Kedaigle AJ, Simmons SK, et al. Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature. 2019 June 01;570(7762):523–527.
  • Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet. 2018 Nov;19(11):671–687. PubMed PMID: 30228295.
  • Sasai Y. Cytosystems dynamics in self-organization of tissue architecture. Nature. 2013 Jan 17;493(7432):318–326. PubMed PMID: 23325214.
  • Assawachananont J, Mandai M, Okamoto S, et al. Transplantation of embryonic and induced pluripotent stem cell-derived 3D retinal sheets into retinal degenerative mice. Stem Cell Reports. 2014 May 6;2(5):662–674. PubMed PMID: 24936453; PubMed Central PMCID: PMCPMC4050483.
  • Freedman BS, Brooks CR, Lam AQ, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun. 2015 Oct;23(6):8715. PubMed PMID: 26493500; PubMed Central PMCID: PMCPMC4620584.
  • Jo J, Xiao Y, Sun AX, et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell. 2016 Aug 4;19(2):248–257. PubMed PMID: 27476966; PubMed Central PMCID: PMCPMC5510242.
  • Lancaster MA, Renner M, Martin CA, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013 Sep 19;501(7467):373–379. PubMed PMID: 23995685; PubMed Central PMCID: PMCPMC3817409.
  • Spence JR, Mayhew CN, Rankin SA, et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011 Feb 3;470(7332):105–109. PubMed PMID: 21151107; PubMed Central PMCID: PMCPMC3033971.
  • Takebe T, Sekine K, Enomura M, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013 Jul 25;499(7459):481–484. PubMed PMID: 23823721.
  • Kim H, Park HJ, Choi H, et al. Modeling G2019S-LRRK2 sporadic Parkinson’s disease in 3D midbrain organoids. Stem Cell Reports. 2019 Mar 5;12(3):518–531. PubMed PMID: 30799274; PubMed Central PMCID: PMCPMC6410341.
  • Birey F, Andersen J, Makinson CD, et al. Assembly of functionally integrated human forebrain spheroids. Nature. 2017 May 4;545(7652):54–59. PubMed PMID: 28445465; PubMed Central PMCID: PMCPMC5805137.
  • Woolsey TA, Van der Loos H. The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res. 1970 Jan 20;17(2):205–242. PubMed PMID: 4904874.
  • Pasca SP. The rise of three-dimensional human brain cultures. Nature. 2018 Jan 24;553(7689):437–445. PubMed PMID: 29364288.
  • Zhang BY, Korolj A, Lai BFL, et al. Advances in organ-on-a-chip engineering. Nat Rev Mater. 2018 Aug;3(8):257–278. PubMed PMID: WOS:000441095600006; English.
  • Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015 Aug 29;386(9996):896–912. PubMed PMID: 25904081.
  • Spillantini MG, Schmidt ML, Lee VM, et al. Alpha-synuclein in Lewy bodies. Nature. 1997 Aug 28;388(6645):839–840. PubMed PMID: 9278044.
  • Lewis SJ, Foltynie T, Blackwell AD, et al. Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry. 2005 Mar;76(3):343–348. PubMed PMID: 15716523; PubMed Central PMCID: PMCPMC1739569.
  • Vidailhet M. Heterogeneity of Parkinson’s disease. Bull Acad Natl Med. 2003;187(2):259–275. discussion 275-6. PubMed PMID: 14556440.
  • Nguyen M, Wong YC, Ysselstein D, et al. Synaptic, mitochondrial, and lysosomal dysfunction in Parkinson’s disease. Trends Neurosci. 2018 Nov 30. DOI:10.1016/j.tins.2018.11.001. PubMed PMID: 30509690.
  • Cooper O, Seo H, Andrabi S, et al. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson’s disease. Sci Transl Med. 2012 Jul 4;4(141):141ra90. PubMed PMID: 22764206; PubMed Central PMCID: PMCPMC3462009.
  • Bogetofte H, Jensen P, Ryding M, et al. PARK2 mutation causes metabolic disturbances and impaired survival of human iPSC-derived neurons. Front Cell Neurosci. 2019;13:297. . PubMed PMID: 31333417; eng.
  • Wong YC, Krainc D. alpha-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat Med. 2017 Feb 7;23(2):1–13. PubMed PMID: 28170377.
  • Lashuel HA, Overk CR, Oueslati A, et al. The many faces of alpha-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2013 Jan;14(1):38–48. PubMed PMID: 23254192; PubMed Central PMCID: PMCPMC4295774.
  • Theillet FX, Binolfi A, Bekei B, et al. Structural disorder of monomeric alpha-synuclein persists in mammalian cells. Nature. 2016 Feb 4;530(7588):45–50. PubMed PMID: 26808899.
  • Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997 Jun 27;276(5321):2045–2047. PubMed PMID: 9197268.
  • Singleton AB, Farrer M, Johnson J, et al. Alpha-synuclein locus triplication causes Parkinson’s disease. Science. 2003 Oct 31;302(5646):841. PubMed PMID: 14593171.
  • Ryan SD, Dolatabadi N, Chan SF, et al. Isogenic human iPSC Parkinson’s model shows nitrosative stress-induced dysfunction in MEF2-PGC1alpha transcription. Cell. 2013 Dec 5;155(6):1351–1364. PubMed PMID: 24290359; PubMed Central PMCID: PMCPMC4028128.
  • Kouroupi G, Taoufik E, Vlachos IS, et al. Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson’s disease. Proc Natl Acad Sci U S A. 2017 May 2;114(18):E3679–E3688. PubMed PMID: 28416701; PubMed Central PMCID: PMCPMC5422768.
  • Dettmer U, Newman AJ, Soldner F, et al. Parkinson-causing alpha-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation. Nat Commun. 2015 Jun;16(6):7314. PubMed PMID: 26076669; PubMed Central PMCID: PMCPMC4490410.
  • Devine MJ, Ryten M, Vodicka P, et al. Parkinson’s disease induced pluripotent stem cells with triplication of the alpha-synuclein locus. Nat Commun. 2011 Aug;2. DOI:10.1038/ncomms1453. ARTN 440. PubMed PMID: WOS:000294806500033; English.
  • Byers B, Cord B, Nguyen HN, et al. SNCA triplication Parkinson’s patient’s iPSC-derived DA neurons accumulate alpha-synuclein and are susceptible to oxidative stress. PLoS One. 2011;6(11):e26159. PubMed PMID: 22110584; PubMed Central PMCID: PMCPMC3217921.
  • Mazzulli JR, Zunke F, Isacson O, et al. Alpha-synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1931–1936. PubMed PMID: 26839413; PubMed Central PMCID: PMCPMC4763774.
  • Ludtmann MHR, Angelova PR, Horrocks MH, et al. alpha-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease. Nat Commun. 2018 Jun 12;9. DOI:10.1038/s41467-018-04422-2 ARTN 2293. PubMed PMID: WOS:000434927000002; English.
  • Heman-Ackah SM, Manzano R, Hoozemans JJM, et al. Alpha-synuclein induces the unfolded protein response in Parkinson’s disease SNCA triplication iPSC-derived neurons. Hum Mol Genet. 2017 Nov 15;26(22):4441–4450. PubMed PMID: WOS:000414403900012; English.
  • Paillusson S, Gomez-Suaga P, Stoica R, et al. Alpha-synuclein binds to the ER-mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production. Acta Neuropathol. 2017 Jul;134(1):129–149. PubMed PMID: WOS:000403235900009; English.
  • Oliveira LMA, Falomir-Lockhart LJ, Botelho MG, et al. Elevated alpha-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson’s patient-derived induced pluripotent stem cells. Cell Death Dis. 2015 Nov;6(6):e1994-e1994. ARTN e1994. PubMed PMID: WOS:000367155300027; English.
  • Zambon F, Cherubini M, Fernandes HJR, et al. Cellular alpha-synuclein pathology is associated with bioenergetic dysfunction in Parkinson’s iPSC-derived dopamine neurons. Hum Mol Genet. 2019 Jun 15;28(12):2001–2013. PubMed PMID: WOS:000475887900006; English.
  • Shaltouki A, Hsieh CH, Kim MJ, et al. Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson’s models. Acta Neuropathol. 2018 Oct;136(4):607–620. PubMed PMID: WOS:000443549100007; English.
  • Prots I, Grosch J, Brazdis RM, et al. Alpha-synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies. Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):7813–7818. PubMed PMID: WOS:000439574700065; English.
  • Chung CY, Khurana V, Auluck PK, et al. Identification and rescue of alpha-synuclein toxicity in Parkinson patient-derived neurons. Science. 2013 Nov 22;342(6161):983–987. PubMed PMID: 24158904; PubMed Central PMCID: PMCPMC4022187.
  • Guaitoli G, Raimondi F, Gilsbach BK, et al. Structural model of the dimeric Parkinson’s protein LRRK2 reveals a compact architecture involving distant interdomain contacts. Proc Nat Acad Sci. 2016;113(30):E4357.
  • Kawakami F, Yabata T, Ohta E, et al. LRRK2 phosphorylates tubulin-associated tau but not the free molecule: LRRK2-mediated regulation of the tau-tubulin association and neurite outgrowth. PLoS One. 2012;7(1):e30834. PubMed PMID: 22303461; PubMed Central PMCID: PMCPMC3267742.
  • Ohta E, Kawakami F, Kubo M, et al. Dominant-negative effects of LRRK2 heterodimers: a possible mechanism of neurodegeneration in Parkinson’s disease caused by LRRK2 I2020T mutation. Biochem Biophys Res Commun. 2013 Jan 11;430(2):560–566. PubMed PMID: 23220480.
  • Reinhardt P, Schmid B, Burbulla LF, et al. Genetic correction of a LRRK2 mutation in human iPSCs links parkinsonian neurodegeneration to ERK-dependent changes in gene expression. Cell Stem Cell. 2013 Mar 7;12(3):354–367. PubMed PMID: 23472874.
  • Steger M, Tonelli F, Ito G, et al. Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. 2016 Jan 29;5. DOI:10.7554/eLife.12813 PubMed PMID: 26824392; PubMed Central PMCID: PMCPMC4769169.
  • Parisiadou L, Xie CS, Cho HJ, et al. Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis. J Neurosci. 2009 Nov 4;29(44):13971–13980. PubMed PMID: WOS:000271471400023; English.
  • Cookson MR. The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson’s disease. Nat Rev Neurosci. 2010 Dec;11(12):791–797. PubMed PMID: 21088684; PubMed Central PMCID: PMCPMC4662256.
  • Orenstein SJ, Kuo SH, Tasset I, et al. Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci. 2013 Apr;16(4):394–406. PubMed PMID: 23455607; PubMed Central PMCID: PMCPMC3609872.
  • Sandor C, Robertson P, Lang C, et al. Transcriptomic profiling of purified patient-derived dopamine neurons identifies convergent perturbations and therapeutics for Parkinson’s disease. Hum Mol Genet. 2017 Feb 1;26(3):552–566. PubMed PMID: WOS:000397067000009; English.
  • Tolosa E, Botta-Orfila T, Morato X, et al. MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients. Neurobiol Aging. 2018 Sep;69:283–291. PubMed PMID: WOS:000439651000029; English.
  • Fernandez-Santiago R, Merkel A, Castellano G, et al. Whole-genome DNA hyper-methylation in iPSC-derived dopaminergic neurons from Parkinson’s disease patients. Clin Epigenetics. 2019 Jul 23;11. DOI:10.1186/s13148-019-0701-6 ARTN 108. PubMed PMID: WOS:000477062600002; English.
  • de Maturana RL, Lang V, Zubiarrain A, et al. Mutations in LRRK2 impair NF-kappa B pathway in iPSC-derived neurons. J Neuroinflammation. 2016 Nov 18;13. DOI:10.1186/s12974-016-0761-x ARTN 295. PubMed PMID: WOS:000390714000001; English.
  • Lin L, Goke J, Cukuroglu E, et al. Molecular features underlying neurodegeneration identified through in vitro modeling of genetically diverse Parkinson’s disease patients. Cell Rep. 2016 Jun 14;15(11):2411–2426. PubMed PMID: 27264186.
  • Borgs L, Peyre E, Alix P, et al. Dopaminergic neurons differentiating from LRRK2 G2019S induced pluripotent stem cells show early neuritic branching defects. Sci Rep. 2016 Sep;19(6):33377. . PubMed PMID: 27640816; PubMed Central PMCID: PMCPMC5027571 Region (SPW) and UCB pharma SA (Convention No. 1217666).
  • Hsieh CH, Shaltouki A, Gonzalez AE, et al. Functional Impairment in Miro degradation and mitophagy is a shared feature in familial and sporadic Parkinson’s disease. Cell Stem Cell. 2016 Dec 1;19(6):709–724. PubMed PMID: 27618216; PubMed Central PMCID: PMCPMC5135570.
  • Sanchez-Danes A, Richaud-Patin Y, Carballo-Carbajal I, et al. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol Med. 2012 May;4(5):380–395. PubMed PMID: 22407749; PubMed Central PMCID: PMCPMC3403296.
  • Sanders LH, Laganiere J, Cooper O, et al. LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson’s disease patients: reversal by gene correction. Neurobiol Dis. 2014 Feb;62:381–386. PubMed PMID: 24148854; PubMed Central PMCID: PMCPMC3877733.
  • Skibinski G, Nakamura K, Cookson MR, et al. Mutant LRRK2 toxicity in neurons depends on LRRK2 levels and synuclein but not kinase activity or inclusion bodies. J Neurosci. 2014 Jan 8;34(2):418–433. PubMed PMID: 24403142; PubMed Central PMCID: PMCPMC3870929.
  • Nguyen HN, Byers B, Cord B, et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell. 2011 Mar 4;8(3):267–280. PubMed PMID: 21362567; PubMed Central PMCID: PMCPMC3578553.
  • Nguyen M, Krainc D. LRRK2 phosphorylation of auxilin mediates synaptic defects in dopaminergic neurons from patients with Parkinson’s disease. Proc Natl Acad Sci U S A. 2018 May 22;115(21):5576–5581. PubMed PMID: 29735704.
  • Greene AW, Grenier K, Aguileta MA, et al. Mitochondrial processing peptidase regulates PINK1 processing, import and Parkin recruitment. EMBO Rep. 2012 Apr;13(4):378–385. PubMed PMID: 22354088; PubMed Central PMCID: PMCPMC3321149.
  • Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson’s disease. Neuron. 2010 Jun 10;66(5):646–661. PubMed PMID: 20547124; PubMed Central PMCID: PMCPMC2917798.
  • Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015 Jan 21;85(2):257–273. PubMed PMID: 25611507; PubMed Central PMCID: PMCPMC4764997.
  • Zeng XS, Geng WS, Jia JJ, et al. Cellular and molecular basis of neurodegeneration in Parkinson disease. Front Aging Neurosci. 2018;10:109. PubMed PMID: 29719505; PubMed Central PMCID: PMCPMC5913322.
  • Durcan TM, Fon EA. The three ‘P’s of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 2015 May 15;29(10):989–999. PubMed PMID: 25995186; PubMed Central PMCID: PMCPMC4441056.
  • Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605–608. PubMed PMID: 9560156.
  • Shimura H, Hattori N, Kubo S, et al. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000 Jul;25(3):302–305. PubMed PMID: 10888878.
  • Seibler P, Graziotto J, Jeong H, et al. Mitochondrial Parkin recruitment is impaired in neurons derived from mutant PINK1 induced pluripotent stem cells. J Neurosci. 2011 Apr 20;31(16):5970–5976. PubMed PMID: WOS:000289769400011; English.
  • Puschmann A, Fiesel FC, Caulfield TR, et al. Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism. Brain. 2017 Jan;140(1):98–117. PubMed PMID: 27807026; PubMed Central PMCID: PMCPMC5379862.
  • Oh CK, Sultan A, Platzer J, et al. S-nitrosylation of PINK1 attenuates PINK1/Parkin-dependent mitophagy in hiPSC-based Parkinson’s disease models. Cell Rep. 2017 Nov 21;21(8):2171–2182. PubMed PMID: WOS:000416216700014; English.
  • Vos M, Geens A, Bohm C, et al. Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency. J Cell Biol. 2017 Mar;216(3):695–708. PubMed PMID: WOS:000395826200020; English.
  • Shaltouki A, Sivapatham R, Pei Y, et al. Mitochondrial alterations by PARKIN in dopaminergic neurons using PARK2 patient-specific and PARK2 knockout isogenic iPSC lines. Stem Cell Rep. 2015 May 12;4(5):847–859. PubMed PMID: WOS:000354406400008; English.
  • Zanon A, Kalvakuri S, Rakovic A, et al. SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and drosophila. Hum Mol Genet. 2017 Jul 1;26(13):2412–2425. PubMed PMID: WOS:000403460700004; English.
  • Gautier CA, Erpapazoglou Z, Mouton-Liger F, et al. The endoplasmic reticulum-mitochondria interface is perturbed in PARK2 knockout mice and patients with PARK2 mutations. Hum Mol Genet. 2016 Jul 15;25(14):2972–2984. PubMed PMID: WOS:000393066300007; English.
  • Ren Q, Ma M, Yang J, et al. Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson’s disease. Proc Natl Acad Sci U S A. 2018 Jun 19;115(25):E5815–E5823. PubMed PMID: WOS:000435585200023; English.
  • Chung SY, Kishinevsky S, Mazzulli JR, et al. Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and alpha-synuclein accumulation. Stem Cell Rep. 2016 Oct 11;7(4):664–677. PubMed PMID: WOS:000389508600007; English.
  • Valadas JS, Esposito G, Vandekerkhove D, et al. ER lipid defects in neuropeptidergic neurons impair sleep patterns in Parkinson’s disease. Neuron. 2018 Jun 27;98(6):1155-+. PubMed PMID: WOS:000436587600015; English.
  • Jiang H, Ren Y, Yuen EY, et al. Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun. 2012 Feb;7(3):668. PubMed PMID: 22314364; PubMed Central PMCID: PMCPMC3498452.
  • Ren Y, Jiang H, Ma D, et al. Parkin degrades estrogen-related receptors to limit the expression of monoamine oxidases. Hum Mol Genet. 2011 Mar 15;20(6):1074–1083. PubMed PMID: 21177257; PubMed Central PMCID: PMCPMC3043659.
  • Zhong P, Hu Z, Jiang H, et al. Dopamine induces oscillatory activities in human midbrain neurons with Parkin mutations. Cell Rep. 2017 May 2;19(5):1033–1044. PubMed PMID: 28467897; PubMed Central PMCID: PMCPMC5492970.
  • Neumann J, Bras J, Deas E, et al. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson’s disease. Brain. 2009 Jul;132(Pt 7):1783–1794. PubMed PMID: 19286695; PubMed Central PMCID: PMCPMC2702833.
  • Gegg ME, Burke D, Heales SJ, et al. Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains. Ann Neurol. 2012 Sep;72(3):455–463. PubMed PMID: 23034917; PubMed Central PMCID: PMCPMC3638323.
  • Mazzulli JR, Xu YH, Sun Y, et al. Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011 Jul 8;146(1):37–52. PubMed PMID: 21700325; PubMed Central PMCID: PMCPMC3132082.
  • Murphy KE, Gysbers AM, Abbott SK, et al. Reduced glucocerebrosidase is associated with increased alpha-synuclein in sporadic Parkinson’s disease. Brain. 2014 Mar;137(Pt 3):834–848. PubMed PMID: 24477431; PubMed Central PMCID: PMCPMC3927701.
  • Wong YC, Krainc D. Lysosomal trafficking defects link Parkinson’s disease with Gaucher’s disease. Mov Disord. 2016 Nov;31(11):1610–1618. . PubMed PMID: 27619775.
  • Schapira AH. Glucocerebrosidase and Parkinson disease: recent advances. Mol Cell Neurosci. 2015 May;66(Pt A):37–42. PubMed PMID: 25802027; PubMed Central PMCID: PMCPMC4471139.
  • Sidransky E, Nalls MA, Aasly JO, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med. 2009 Oct 22;361(17):1651–1661. PubMed PMID: 19846850; PubMed Central PMCID: PMCPMC2856322.
  • Gan-Or Z, Bar-Shira A, Mirelman A, et al. LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease. Neurogenetics. 2010 Feb;11(1):121–125. PubMed PMID: 19458969.
  • Lesage S, Anheim M, Condroyer C, et al. Large-scale screening of the Gaucher’s disease-related glucocerebrosidase gene in Europeans with Parkinson’s disease. Hum Mol Genet. 2011 Jan 1;20(1):202–210. PubMed PMID: 20947659.
  • Cilia R, Tunesi S, Marotta G, et al. Survival and dementia in GBA-associated Parkinson’s disease: the mutation matters. Ann Neurol. 2016 Nov;80(5):662–673. PubMed PMID: 27632223.
  • Oeda T, Umemura A, Mori Y, et al. Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson’s disease. Neurobiol Aging. 2015 Dec;36(12):3306–3313. PubMed PMID: 26422360.
  • Thaler A, Gurevich T, Bar Shira A, et al. A “dose” effect of mutations in the GBA gene on Parkinson’s disease phenotype. Parkinsonism Relat Disord. 2017 Mar;36:47–51. PubMed PMID: 28012950.
  • Aflaki E, Borger DK, Moaven N, et al. A new glucocerebrosidase chaperone reduces alpha-synuclein and glycolipid levels in iPSC-derived dopaminergic neurons from patients with gaucher disease and parkinsonism. J Neurosci. 2016 Jul 13;36(28):7441–7452. PubMed PMID: 27413154; PubMed Central PMCID: PMCPMC4945664.
  • Kim S, Yun SP, Lee S, et al. GBA1 deficiency negatively affects physiological alpha-synuclein tetramers and related multimers. Proc Natl Acad Sci U S A. 2018 Jan 23;115(4):798–803. PubMed PMID: 29311330; PubMed Central PMCID: PMCPMC5789900.
  • Schondorf DC, Aureli M, McAllister FE, et al. iPSC-derived neurons from GBA1-associated Parkinson’s disease patients show autophagic defects and impaired calcium homeostasis. Nat Commun. 2014 Jun;6(5):4028. PubMed PMID: 24905578.
  • Fernandes HJ, Hartfield EM, Christian HC, et al. ER stress and autophagic perturbations lead to elevated extracellular alpha-synuclein in GBA-N370S Parkinson’s iPSC-derived dopamine neurons. Stem Cell Reports. 2016 Mar 8;6(3):342–356. PubMed PMID: 26905200; PubMed Central PMCID: PMCPMC4788783.
  • Woodard CM, Campos BA, Kuo SH, et al. iPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson’s disease. Cell Rep. 2014 Nov 20;9(4):1173–1182. PubMed PMID: 25456120; PubMed Central PMCID: PMCPMC4255586.
  • Mazzulli JR, Zunke F, Tsunemi T, et al. Activation of beta-glucocerebrosidase reduces pathological alpha-synuclein and restores lysosomal function in Parkinson’s patient midbrain neurons. J Neurosci. 2016 Jul 20;36(29):7693–7706. PubMed PMID: 27445146; PubMed Central PMCID: PMCPMC4951575.
  • Schondorf DC, Ivanyuk D, Baden P, et al. The NAD+ precursor nicotinamide riboside rescues mitochondrial defects and neuronal loss in iPSC and fly models of Parkinson’s disease. Cell Rep. 2018 Jun 5;23(10):2976–2988. PubMed PMID: 29874584.
  • Burbulla LF, Jeon S, Zheng J, et al. A modulator of wild-type glucocerebrosidase improves pathogenic phenotypes in dopaminergic neuronal models of Parkinson’s disease. Sci Transl Med. 2019 Oct 16;11(514):eaau6870. PubMed PMID: 31619543.
  • Lang C, Campbell KR, Ryan BJ, et al. Single-cell sequencing of iPSC-dopamine neurons reconstructs disease progression and identifies HDAC4 as a regulator of parkinson cell phenotypes. Cell Stem Cell. 2019 Jan 3;24(1):93-+. PubMed PMID: WOS:000454836900012; English.
  • Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003 Jan 10;299(5604):256–259. PubMed PMID: 12446870.
  • Ramirez A, Heimbach A, Grundemann J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet. 2006 Oct;38(10):1184–1191. PubMed PMID: 16964263.
  • Mc Donald JM, Krainc D. Lysosomal proteins as a therapeutic target in neurodegeneration. Annu Rev Med. 2017 Jan 14;68:445–458. PubMed PMID: 28099085.
  • Tsunemi T, Hamada K, Krainc D. ATP13A2/PARK9 regulates secretion of exosomes and alpha-synuclein. J Neurosci. 2014 Nov 12;34(46):15281–15287. . PubMed PMID: 25392495; PubMed Central PMCID: PMCPMC4228131.
  • Tsunemi T, Perez-Rosello T, Ishiguro Y, et al. Increased lysosomal exocytosis induced by lysosomal Ca(2+) channel agonists protects human dopaminergic neurons from alpha-synuclein toxicity. J Neurosci. 2019 Jul 17;39(29):5760–5772. PubMed PMID: 31097622; PubMed Central PMCID: PMCPMC6636071.
  • Krebs CE, Karkheiran S, Powell JC, et al. The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive parkinsonism with generalized seizures. Hum Mutat. 2013 Sep;34(9):1200–1207. PubMed PMID: WOS:000323109200004; English.
  • Olgiati S, De Rosa A, Quadri M, et al. PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family. Neurogenetics. 2014 Aug;15(3):183–188. PubMed PMID: WOS:000339892700006; English.
  • Quadri M, Fang M, Picillo M, et al. Mutation in the SYNJ1 gene associated with autosomal recessive, early-onset Parkinsonism. Hum Mutat. 2013 Sep;34(9):1208–1215. PubMed PMID: 23804577.
  • Vanhauwaert R, Kuenen S, Masius R, et al. The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals. Embo J. 2017 May 15;36(10):1392–1411. PubMed PMID: WOS:000401226700008; English.
  • Vilarino-Guell C, Wider C, Ross OA, et al. VPS35 mutations in Parkinson disease. Am J Hum Genet. 2011 Jul 15;89(1):162–167. PubMed PMID: WOS:000293041700015; English.
  • Zimprich A, Benet-Pages A, Struhal W, et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet. 2011 Jul 15;89(1):168–175. PubMed PMID: WOS:000293041700016; English.
  • Munsie LN, Milnerwood AJ, Seibler P, et al. Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson’s disease VPS35 mutation p.D620N. Hum Mol Genet. 2015 Mar 15;24(6):1691–1703. PubMed PMID: WOS:000350144200015; English.
  • Cannon JR, Greenamyre JT. Gene-environment interactions in Parkinson’s disease: specific evidence in humans and mammalian models. Neurobiol Dis. 2013 Sep;57:38–46. PubMed PMID: 22776331; PubMed Central PMCID: PMCPMC3815566.
  • Chai C, Lim KL. Genetic insights into sporadic Parkinson’s disease pathogenesis. Curr Genomics. 2013 Dec;14(8):486–501. PubMed PMID: 24532982; PubMed Central PMCID: PMCPMC3924245.
  • Horowitz MP, Greenamyre JT. Gene-environment interactions in Parkinson’s disease: the importance of animal modeling. Clin Pharmacol Ther. 2010 Oct;88(4):467–474. PubMed PMID: 20811350; PubMed Central PMCID: PMCPMC3085510.
  • Vance JM, Ali S, Bradley WG, et al. Gene-environment interactions in Parkinson’s disease and other forms of parkinsonism. Neurotoxicology. 2010 Sep;31(5):598–602. PubMed PMID: 20430055.
  • Checkoway H, Franklin GM, Costa-Mallen P, et al. A genetic polymorphism of MAO-B modifies the association of cigarette smoking and Parkinson’s disease. Neurology. 1998 May;50(5):1458–1461. PubMed PMID: 9596006.
  • Benmoyal-Segal L, Vander T, Shifman S, et al. Acetylcholinesterase/paraoxonase interactions increase the risk of insecticide-induced Parkinson’s disease. Faseb J. 2005 Mar;19(3):452–454. PubMed PMID: 15629887.
  • Deng Y, Newman B, Dunne MP, et al. Further evidence that interactions between CYP2D6 and pesticide exposure increase risk for Parkinson’s disease. Ann Neurol. 2004 Jun;55(6):897. PubMed PMID: 15174030.
  • Elbaz A, Levecque C, Clavel J, et al. CYP2D6 polymorphism, pesticide exposure, and Parkinson’s disease. Ann Neurol. 2004 Mar;55(3):430–434. PubMed PMID: 14991823.
  • Kelava I, Lancaster MA. Dishing out mini-brains: current progress and future prospects in brain organoid research. Dev Biol. 2016 Dec 15;420(2):199–209. . PubMed PMID: 27402594; PubMed Central PMCID: PMCPMC5161139.
  • Monzel AS, Smits LM, Hemmer K, et al. Derivation of human midbrain-specific organoids from neuroepithelial stem cells. Stem Cell Reports. 2017 May 9;8(5):1144–1154. PubMed PMID: 28416282; PubMed Central PMCID: PMCPMC5425618.
  • Smits LM, Reinhardt L, Reinhardt P, et al. Modeling Parkinson’s disease in midbrain-like organoids. NPJ Parkinsons Dis. 2019;5:5. . PubMed PMID: 30963107; PubMed Central PMCID: PMCPMC6450999.
  • Zheng J, Jeon S, Jiang W, et al. Conversion of quinazoline modulators from inhibitors to activators of beta-glucocerebrosidase. J Med Chem. 2019 Feb 14;62(3):1218–1230. PubMed PMID: 30645117; PubMed Central PMCID: PMCPMC6467782.
  • Kim MJ, Jeon S, Burbulla LF, et al. Acid ceramidase inhibition ameliorates alpha-synuclein accumulation upon loss of GBA1 function. Hum Mol Genet. 2018 Jun 1;27(11):1972–1988. PubMed PMID: 29579237; PubMed Central PMCID: PMCPMC6251682.
  • Zunke F, Moise AC, Belur NR, et al. Reversible conformational conversion of alpha-synuclein into toxic assemblies by glucosylceramide. Neuron. 2018 Jan 3;97(1):92-+. PubMed PMID: WOS:000419224100012; English.
  • Fanning S, Haque A, Imberdis T, et al. Lipidomic analysis of alpha-synuclein neurotoxicity identifies stearoyl CoA desaturase as a target for Parkinson treatment. Mol Cell. 2019 Mar 7;73(5):1001-+. PubMed PMID: WOS:000460545200014; English.
  • Cooper O. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson’s disease. Sci Transl Med. 2012 Jul 4;4(141):141ra90–141ra90. PubMed PMID: WOS:000306108800003; English.
  • Barker RA, Farrell K, Guzman NV, et al. Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease. Nat Med. 2019 Jul;25(7):1045–1053. PubMed PMID: WOS:000474430400016; English.
  • Rhee YH, Ko JY, Chang MY, et al. Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Investig. 2011 Jun;121(6):2326–2335. PubMed PMID: WOS:000291234300031; English.
  • Gonzalez R, Garitaonandia I, Poustovoitov M, et al. Neural stem cells derived from human parthenogenetic stem cells engraft and promote recovery in a nonhuman primate model of Parkinson’s disease. Cell Transplant. 2016;25(11):1945–1966. . PubMed PMID: WOS:000387774300003; English.
  • Cai JL, Yang M, Poremsky E, et al. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats. Stem Cells Dev. 2010 Jul;19(7):1017–1023. PubMed PMID: WOS:000279976900007; English.
  • Wernig M, Zhao JP, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci U S A. 2008 Apr 15;105(15):5856–5861. PubMed PMID: WOS:000255237200038; English.
  • Hargus G, Cooper O, Deleidi M, et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in parkinsonian rats. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15921–15926. PubMed PMID: WOS:000281637800054; English.
  • Hallett PJ, Deleidi M, Astradsson A, et al. Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson’s disease. Cell Stem Cell. 2015 Mar 5;16(3):269–274. PubMed PMID: WOS:000350747700009; English.
  • Nussbaum RL, Ellis CE. Alzheimer’s disease and Parkinson’s disease. N Engl J Med. 2003 Apr 3;348(14):1356–1364. PubMed PMID: 12672864.
  • Tanner CM, Goldman SM. Epidemiology of Parkinson’s disease. Neurol Clin. 1996 May;14(2):317–335. PubMed PMID: 8827174.
  • Burbulla LF, Beaumont KG, Mrksich M, et al. micropatterning facilitates the long-term growth and analysis of iPSC-derived individual human neurons and neuronal networks. Adv Healthc Mater. 2016 Aug;5(15):1894–1903. PubMed PMID: 27108930; PubMed Central PMCID: PMCPMC4982819.
  • Zhu L, Sun C, Ren J, et al. Stress-induced precocious aging in PD-patient iPSC-derived NSCs may underlie the pathophysiology of Parkinson’s disease. Cell Death Dis. 2019 Feb 04;10(2):105. .
  • Miller JD, Ganat YM, Kishinevsky S, et al. Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell. 2013 Dec 5;13(6):691–705. PubMed PMID: 24315443; PubMed Central PMCID: PMCPMC4153390.
  • Lapasset L, Milhavet O, Prieur A, et al. Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes Dev. 2011 Nov 1;25(21):2248–2253. PubMed PMID: 22056670; PubMed Central PMCID: PMCPMC3219229.
  • Marion RM, Strati K, Li H, et al. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell. 2009 Feb 6;4(2):141–154. PubMed PMID: 19200803.
  • Suhr ST, Chang EA, Tjong J, et al. Mitochondrial rejuvenation after induced pluripotency. PLoS One. 2010 Nov 23;5(11):e14095. PubMed PMID: 21124794; PubMed Central PMCID: PMCPMC2991355.
  • Fiesel FC, Ando M, Hudec R, et al. (Patho-)physiological relevance of PINK1-dependent ubiquitin phosphorylation. EMBO Rep. 2015 Sep;16(9):1114–1130. PubMed PMID: 26162776; PubMed Central PMCID: PMCPMC4576981.
  • Drouin-Ouellet J, Lau S, Brattas PL, et al. REST suppression mediates neural conversion of adult human fibroblasts via microRNA-dependent and -independent pathways. EMBO Mol Med. 2017 Aug;9(8):1117–1131. PubMed PMID: 28646119; PubMed Central PMCID: PMCPMC5538296.
  • International Parkinson Disease Genomics C, Nalls MA, Plagnol V, Hernandez DG, et al. Imputation of sequence variants for identification of genetic risks for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet. 2011 Feb 19;377(9766):641–649. PubMed PMID: 21292315; PubMed Central PMCID: PMCPMC3696507.
  • Vierbuchen T, Ostermeier A, Pang ZP, et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010 Feb 25;463(7284):1035–1041. PubMed PMID: 20107439; PubMed Central PMCID: PMCPMC2829121.
  • Zhang Y, Pak C, Han Y, et al. Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron. 2013 Jun 5;78(5):785–798. PubMed PMID: 23764284; PubMed Central PMCID: PMCPMC3751803.
  • Khurana V, Peng J, Chung CY, et al. Genome-scale networks link neurodegenerative disease genes to alpha-synuclein through specific molecular pathways. Cell Syst. 2017 Feb 22;4(2):157-+. PubMed PMID: WOS:000395786100008; English.
  • Mariani J, Simonini MV, Palejev D, et al. Modeling human cortical development in vitro using induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12770–12775. PubMed PMID: 22761314; PubMed Central PMCID: PMCPMC3411972.
  • Schwank G, Koo B-K, Sasselli V, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013 Dec 05;13(6):653–658. .
  • Choi SH, Kim YH, Hebisch M, et al. A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature. 2014 Nov 13;515(7526):274–278. PubMed PMID: 25307057; PubMed Central PMCID: PMCPMC4366007.
  • Phan DT, Bender RHF, Andrejecsk JW, et al. Blood-brain barrier-on-a-chip: microphysiological systems that capture the complexity of the blood-central nervous system interface. Exp Biol Med (Maywood). 2017 Nov;242(17):1669–1678. PubMed PMID: 28195514; PubMed Central PMCID: PMCPMC5786363.
  • Yoon SJ, Elahi LS, Pasca AM, et al. Reliability of human cortical organoid generation. Nat Methods. 2019 Jan;16(1):75-+. PubMed PMID: WOS:000454162400033; English.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.