Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912. https://doi.org/10.1016/S0140-6736(14)61393-3

Article  CAS  PubMed  Google Scholar 

Kikuchi T, Morizane A, Doi D, Magotani H, Onoe H, Hayashi T, Mizuma H, Takara S, Takahashi R, Inoue H, Morita S, Yamamoto M, Okita K, Nakagawa M, Parmar M, Takahashi J (2017) Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 548:592–596. https://doi.org/10.1038/nature23664

Article  CAS  PubMed  Google Scholar 

Lonskaya I, Hebron ML, Desforges NM, Schachter JB, Moussa CE (2014) Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance. J Mol Med (Berl) 92:373–386. https://doi.org/10.1007/s00109-013-1112-3

Article  CAS  PubMed  Google Scholar 

Zheng N, Shabek N (2017) Ubiquitin ligases: structure, function, and regulation. Annu Rev Biochem 86:129–157. https://doi.org/10.1146/annurev-biochem-060815-014922

Article  CAS  PubMed  Google Scholar 

Yau RG, Doerner K, Castellanos ER, Haakonsen DL, Werner A, Wang N, Yang XW, Martinez-Martin N, Matsumoto ML, Dixit VM, Rape M (2017) Assembly and function of heterotypic ubiquitin chains in cell-cycle and protein quality control. Cell 171(918–933):e20. https://doi.org/10.1016/j.cell.2017.09.040

Article  CAS  Google Scholar 

Schmidt MF, Gan ZY, Komander D, Dewson G (2021) Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities. Cell Death Differ 28:570–590. https://doi.org/10.1038/s41418-020-00706-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee JH, Shin SK, Jiang Y, Choi WH, Hong C, Kim DE, Lee MJ (2015) Facilitated Tau degradation by USP14 aptamers via enhanced proteasome activity. Sci Rep 5:10757. https://doi.org/10.1038/srep10757

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang P, Joberty G, Buist A, Vanoosthuyse A, Stancu IC, Vasconcelos B, Pierrot N, Faelth-Savitski M, Kienlen-Campard P, Octave JN, Bantscheff M, Drewes G, Moechars D, Dewachter I (2017) Tau interactome mapping based identification of Otub1 as Tau deubiquitinase involved in accumulation of pathological Tau forms in vitro and in vivo. Acta Neuropathol 133:731–749. https://doi.org/10.1007/s00401-016-1663-9

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu X, Hebron M, Shi W, Lonskaya I, Moussa CE (2019) Ubiquitin specific protease-13 independently regulates parkin ubiquitination and alpha-synuclein clearance in alpha-synucleinopathies. Hum Mol Genet 28:548–560. https://doi.org/10.1093/hmg/ddy365

Article  CAS  PubMed  Google Scholar 

Alexopoulou Z, Lang J, Perrett RM, Elschami M, Hurry ME, Kim HT, Mazaraki D, Szabo A, Kessler BM, Goldberg AL, Ansorge O, Fulga TA, Tofaris GK (2016) Deubiquitinase Usp8 regulates alpha-synuclein clearance and modifies its toxicity in Lewy body disease. Proc Natl Acad Sci U S A 113:E4688–E4697. https://doi.org/10.1073/pnas.1523597113

Article  CAS  PubMed  PubMed Central  Google Scholar 

Du XY, Xie XX, Liu RT (2020) The role of alpha-synuclein oligomers in Parkinson’s disease. Int J Mol Sci. https://doi.org/10.3390/ijms21228645

Article  PubMed  PubMed Central  Google Scholar 

Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka K, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S (2011) A more efficient method to generate integration-free human iPS cells. Nat Methods 8:409–412. https://doi.org/10.1038/nmeth.1591

Article  CAS  PubMed  Google Scholar 

Li W, Sun W, Zhang Y, Wei W, Ambasudhan R, Xia P, Talantova M, Lin T, Kim J, Wang X, Kim WR, Lipton SA, Zhang K, Ding S (2011) Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors. Proc Natl Acad Sci U S A 108:8299–8304. https://doi.org/10.1073/pnas.1014041108

Article  PubMed  PubMed Central  Google Scholar 

Woodard CM, Campos BA, Kuo SH, Nirenberg MJ, Nestor MW, Zimmer M, Mosharov EV, Sulzer D, Zhou H, Paull D, Clark L, Schadt EE, Sardi SP, Rubin L, Eggan K, Brock M, Lipnick S, Rao M, Chang S, Li A, Noggle SA (2014) iPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson’s disease. Cell Rep 9:1173–1182. https://doi.org/10.1016/j.celrep.2014.10.023

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal MF, Surmeier DJ, Kordower JH, Tabar V, Studer L (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480:547–551. https://doi.org/10.1038/nature10648

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373:2055–2066. https://doi.org/10.1016/S0140-6736(09)60492-X

Article  CAS  PubMed  Google Scholar 

Telenti A, Pierce LC, Biggs WH, di Iulio J, Wong EH, Fabani MM, Kirkness EF, Moustafa A, Shah N, Xie C, Brewerton SC, Bulsara N, Garner C, Metzker G, Sandoval E, Perkins BA, Och FJ, Turpaz Y, Venter JC (2016) Deep sequencing of 10,000 human genomes. Proc Natl Acad Sci U S A 113:11901–11906. https://doi.org/10.1073/pnas.1613365113

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O’Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, Exome Aggregation C (2016) Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–291. https://doi.org/10.1038/nature19057

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lan T, Lin H, Zhu W, Laurent T, Yang M, Liu X, Wang J, Wang J, Yang H, Xu X, Guo X (2017) Deep whole-genome sequencing of 90 Han Chinese genomes. Gigascience 6:1–7. https://doi.org/10.1093/gigascience/gix067

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242. https://doi.org/10.1093/nar/28.1.235

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yachdav G, Kloppmann E, Kajan L, Hecht M, Goldberg T, Hamp T, Honigschmid P, Schafferhans A, Roos M, Bernhofer M, Richter L, Ashkenazy H, Punta M, Schlessinger A, Bromberg Y, Schneider R, Vriend G, Sander C, Ben-Tal N, Rost B (2014) PredictProtein—an open resource for online prediction of protein structural and functional features. Nucleic Acids Res 42:W337–W343. https://doi.org/10.1093/nar/gku366

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang S, Liu YQ, Jia C, Lim YJ, Feng G, Xu E, Long H, Kimura Y, Tao Y, Zhao C, Wang C, Liu Z, Hu JJ, Ma MR, Liu Z, Jiang L, Li D, Wang R, Dawson VL, Dawson TM, Li YM, Mao X, Liu C (2021) Mechanistic basis for receptor-mediated pathological alpha-synuclein fibril cell-to-cell transmission in Parkinson’s disease. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.2011196118

Article  PubMed  PubMed Central  Google Scholar 

Vinueza-Gavilanes R, Inigo-Marco I, Larrea L, Lasa M, Carte B, Santamaria E, Fernandez-Irigoyen J, Bugallo R, Aragon T, Aldabe R, Arrasate M (2020) N-terminal acetylation mutants affect alpha-synuclein stability, protein levels and neuronal toxicity. Neurobiol Dis 137:104781. https://doi.org/10.1016/j.nbd.2020.104781

Article  CAS  PubMed  Google Scholar 

Savyon M, Engelender S (2020) SUMOylation in alpha-synuclein homeostasis and pathology. Front Aging Neurosci 12:167. https://doi.org/10.3389/fnagi.2020.00167

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ryan P, Xu M, Davey AK, Danon JJ, Mellick GD, Kassiou M, Rudrawar S (2019) O-GlcNAc modification protects against protein misfolding and aggregation in neurodegenerative disease. ACS Chem Neurosci 10:2209–2221. https://doi.org/10.1021/acschemneuro.9b00143

Article  CAS  PubMed  Google Scholar 

Bluhm A, Schrempel S, von Horsten S, Schulze A, Rossner S (2021) Proteolytic alpha-synuclein cleavage in health and disease. Int J Mol Sci. https://doi.org/10.3390/ijms22115450

Article  PubMed  PubMed Central  Google Scholar 

Nonaka T, Iwatsubo T, Hasegawa M (2005) Ubiquitination of alpha-synuclein. Biochemistry 44:361–368. https://doi.org/10.1021/bi0485528

Article  CAS  PubMed  Google Scholar 

Burmann BM, Gerez JA, Matecko-Burmann I, Campioni S, Kumari P, Ghosh D, Mazur A, Aspholm EE, Sulskis D, Wawrzyniuk M, Bock T, Schmidt A, Rudiger SGD, Riek R, Hiller S (2020) Regulation of alpha-synuclein by chaperones in mammalian cells. Nature 577:127–132. https://doi.org/10.1038/s41586-019-1808-9

Article  CAS  PubMed  Google Scholar