Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ, Barbour R, Huang J, Kling K, Lee M, Diep L, Keim PS, Shen X, Chataway T, Schlossmacher MG, Seubert P, Schenk D, Sinha S, Gai WP, Chilcote TJ (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 281:29739–29752. https://doi.org/10.1074/jbc.M600933200
Article
CAS
PubMed
Google Scholar
Barrett PJ, Timothy Greenamyre J (2015) Post-translational modification of alpha-synuclein in Parkinson's disease. Brain Res 1628:247–253. https://doi.org/10.1016/j.brainres.2015.06.002
Article
CAS
PubMed
Google Scholar
Becker K, Wang X, Vander Stel K, Chu Y, Kordower J, Ma J (2018) Detecting alpha Synuclein seeding activity in formaldehyde-fixed MSA patient tissue by PMCA. Mol Neurobiol 55:8728–8737. https://doi.org/10.1007/s12035-018-1007-y
Article
CAS
PubMed
PubMed Central
Google Scholar
Billingsley KJ, Bandres-Ciga S, Saez-Atienzar S, Singleton AB (2018) Genetic risk factors in Parkinson's disease. Cell Tissue Res 373:9–20. https://doi.org/10.1007/s00441-018-2817-y
Article
CAS
PubMed
PubMed Central
Google Scholar
Burre J, Sharma M, Sudhof TC (2012) Systematic mutagenesis of alpha-synuclein reveals distinct sequence requirements for physiological and pathological activities. J Neurosci 32:15227–15242. https://doi.org/10.1523/JNEUROSCI.3545-12.2012
Article
CAS
PubMed
PubMed Central
Google Scholar
Burre J, Sharma M, Sudhof TC (2014) Alpha-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. Proc Natl Acad Sci U S A 111:E4274–E4283. https://doi.org/10.1073/pnas.1416598111
Article
CAS
PubMed
PubMed Central
Google Scholar
Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Sudhof TC (2010) Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329:1663–1667. https://doi.org/10.1126/science.1195227
Article
CAS
PubMed
PubMed Central
Google Scholar
Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, Levecque C, Larvor L, Andrieux J, Hulihan M, Waucquier N, Defebvre L, Amouyel P, Farrer M, Destee A (2004) Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364:1167–1169. https://doi.org/10.1016/S0140-6736(04)17103-1
Article
CAS
PubMed
Google Scholar
Chinta SJ, Mallajosyula JK, Rane A, Andersen JK (2010) Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo. Neurosci Lett 486:235–239. https://doi.org/10.1016/j.neulet.2010.09.061
Article
CAS
PubMed
PubMed Central
Google Scholar
Conway KA, Harper JD, Lansbury PT (1998) Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med 4:1318–1320. https://doi.org/10.1038/3311
Article
CAS
PubMed
Google Scholar
Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39:889–909
Article
CAS
Google Scholar
Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK (2008) Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem 283:9089–9100. https://doi.org/10.1074/jbc.M710012200
Article
CAS
PubMed
PubMed Central
Google Scholar
Di Maio R, Barrett PJ, Hoffman EK, Barrett CW, Zharikov A, Borah A, Hu X, McCoy J, Chu CT, Burton EA, Hastings TG, Greenamyre JT (2016) Alpha-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease. Sci Transl Med 8:342ra378. https://doi.org/10.1126/scitranslmed.aaf3634
Article
CAS
Google Scholar
Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T (2002) Alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4:160–164. https://doi.org/10.1038/ncb748
Article
CAS
PubMed
Google Scholar
Goedert M, Jakes R, Spillantini MG (2017) The Synucleinopathies: twenty years on. J Park Dis 7:S53–S71. https://doi.org/10.3233/JPD-179005
Article
Google Scholar
Guardia-Laguarta C, Area-Gomez E, Rub C, Liu Y, Magrane J, Becker D, Voos W, Schon EA, Przedborski S (2014) Alpha-Synuclein is localized to mitochondria-associated ER membranes. J Neurosci 34:249–259. https://doi.org/10.1523/JNEUROSCI.2507-13.2014
Article
CAS
PubMed
PubMed Central
Google Scholar
Halliday GM, Holton JL, Revesz T, Dickson DW (2011) Neuropathology underlying clinical variability in patients with synucleinopathies. Acta Neuropathol 122:187–204. https://doi.org/10.1007/s00401-011-0852-9
Article
CAS
PubMed
Google Scholar
Iwai A, Masliah E, Yoshimoto M, Ge N, Flanagan L, de Silva HA, Kittel A, Saitoh T (1995) The precursor protein of non-a beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron 14:467–475
Article
CAS
Google Scholar
Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345:27–32
Article
CAS
Google Scholar
Janezic S, Threlfell S, Dodson PD, Dowie MJ, Taylor TN, Potgieter D, Parkkinen L, Senior SL, Anwar S, Ryan B, Deltheil T, Kosillo P, Cioroch M, Wagner K, Ansorge O, Bannerman DM, Bolam JP, Magill PJ, Cragg SJ, Wade-Martins R (2013) Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model. Proc Natl Acad Sci U S A 110:E4016–E4025. https://doi.org/10.1073/pnas.1309143110
Article
CAS
PubMed
PubMed Central
Google Scholar
Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A, Okochi M, Leimer U, van Der Putten H, Probst A, Kremmer E, Kretzschmar HA, Haass C (2000) Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha -synuclein in human and transgenic mouse brain. J Neurosci 20:6365–6373
Article
CAS
Google Scholar
Kopito RR (2000) Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 10:524–530
Article
CAS
Google Scholar
Lashuel HA, Overk CR, Oueslati A, Masliah E (2013) The many faces of alpha-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci 14:38–48. https://doi.org/10.1038/nrn3406
Article
CAS
PubMed
PubMed Central
Google Scholar
Lee MK, Stirling W, Xu Y, Xu X, Qui D, Mandir AS, Dawson TM, Copeland NG, Jenkins NA, Price DL (2002) Human alpha-synuclein-harboring familial Parkinson's disease-linked ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc Natl Acad Sci U S A 99:8968–8973. https://doi.org/10.1073/pnas.132197599
Article
CAS
PubMed
PubMed Central
Google Scholar
Li WW, Yang R, Guo JC, Ren HM, Zha XL, Cheng JS, Cai DF (2007) Localization of alpha-synuclein to mitochondria within midbrain of mice. Neuroreport 18:1543–1546. https://doi.org/10.1097/WNR.0b013e3282f03db4
Article
CAS
PubMed
Google Scholar
Liu G, Zhang C, Yin J, Li X, Cheng F, Li Y, Yang H, Ueda K, Chan P, Yu S (2009) Alpha-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity. Neurosci Lett 454:187–192. https://doi.org/10.1016/j.neulet.2009.02.056
Article
CAS
PubMed
Google Scholar
Ludtmann MH, Angelova PR, Ninkina NN, Gandhi S, Buchman VL, Abramov AY (2016) Monomeric alpha-Synuclein exerts a physiological role on brain ATP synthase. J Neurosci 36:10510–10521. https://doi.org/10.1523/JNEUROSCI.1659-16.2016
Article
CAS
PubMed
PubMed Central
Google Scholar
Ludtmann MHR, Angelova PR, Horrocks MH, Choi ML, Rodrigues M, Baev AY, Berezhnov AV, Yao Z, Little D, Banushi B, Al-Menhali AS, Ranasinghe RT, Whiten DR, Yapom R, Dolt KS, Devine MJ, Gissen P, Kunath T, Jaganjac M, Pavlov EV, Klenerman D, Abramov AY, Gandhi S (2018) Alpha-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson's disease. Nat Commun 9:2293. https://doi.org/10.1038/s41467-018-04422-2
Article
CAS
PubMed
PubMed Central
Google Scholar
Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM (2012) Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338:949–953. https://doi.org/10.1126/science.1227157
Article
CAS
PubMed
PubMed Central
Google Scholar
Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA, Price DL, Lee MK (2006) Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci 26:41–50. https://doi.org/10.1523/JNEUROSCI.4308-05.2006
Article
CAS
PubMed
PubMed Central
Google Scholar
Olanow CW, Perl DP, DeMartino GN, McNaught KS (2004) Lewy-body formation is an aggresome-related process: a hypothesis. Lancet Neurol 3:496–503. https://doi.org/10.1016/S1474-4422(04)00827-0
Article
PubMed
Google Scholar
Olgiati S, Thomas A, Quadri M, Breedveld GJ, Graafland J, Eussen H, Douben H, de Klein A, Onofrj M, Bonifati V (2015) Early-onset parkinsonism caused by alpha-synuclein gene triplication: clinical and genetic findings in a novel family. Parkinsonism Relat Disord 21:981–986. https://doi.org/10.1016/j.parkreldis.2015.06.005
Article
PubMed
Google Scholar
Pan T, Kondo S, Le W, Jankovic J (2008) The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease. Brain 131:1969–1978. https://doi.org/10.1093/brain/awm318
Article
PubMed
Google Scholar
Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, Zhang B, Pitkin RM, Olufemi MF, Luk KC, Trojanowski JQ, Lee VM (2018) Cellular milieu imparts distinct pathological alpha-synuclein strains in alpha-synucleinopathies. Nature 557:558–563. https://doi.org/10.1038/s41586-018-0104-4
Article
CAS
PubMed
PubMed Central
Google Scholar
Peng C, Gathagan RJ, Lee VM (2018) Distinct alpha-Synuclein strains and implications for heterogeneity among alpha-Synucleinopathies. Neurobiol Dis 109:209–218. https://doi.org/10.1016/j.nbd.2017.07.018
Article
CAS
PubMed
Google Scholar
Pissadaki EK, Bolam JP (2013) The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease. Front Comput Neurosci 7:13. https://doi.org/10.3389/fncom.2013.00013
Article
PubMed
PubMed Central
Google Scholar
Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nature reviews Disease primers 3:17013. https://doi.org/10.1038/nrdp.2017.13
Article
PubMed
Google Scholar
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276:2045–2047
Article
CAS
Google Scholar
Power JH, Barnes OL, Chegini F (2017) Lewy bodies and the mechanisms of neuronal cell death in Parkinson's disease and dementia with Lewy bodies. Brain Pathol 27:3–12. https://doi.org/10.1111/bpa.12344
Article
CAS
PubMed
Google Scholar
Rideout HJ, Larsen KE, Sulzer D, Stefanis L (2001) Proteasomal inhibition leads to formation of ubiquitin/alpha-synuclein-immunoreactive inclusions in PC12 cells. J Neurochem 78:899–908
Article
CAS
Google Scholar
Rochet JC, Conway KA, Lansbury PT Jr (2000) Inhibition of fibrillization and accumulation of prefibrillar oligomers in mixtures of human and mouse alpha-synuclein. Biochemistry 39:10619–10626
Article
CAS
Google Scholar
Ryan T, Bamm VV, Stykel MG, Coackley CL, Humphries KM, Jamieson-Williams R, Ambasudhan R, Mosser DD, Lipton SA, Harauz G, Ryan SD (2018) Cardiolipin exposure on the outer mitochondrial membrane modulates alpha-synuclein. Nat Commun 9:817. https://doi.org/10.1038/s41467-018-03241-9
Article
CAS
PubMed
PubMed Central
Google Scholar
Sacino AN, Brooks M, Thomas MA, McKinney AB, Lee S, Regenhardt RW, McGarvey NH, Ayers JI, Notterpek L, Borchelt DR, Golde TE, Giasson BI (2014) Intramuscular injection of alpha-synuclein induces CNS alpha-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci U S A 111:10732–10737. https://doi.org/10.1073/pnas.1321785111
Article
CAS
PubMed
PubMed Central
Google Scholar
Shavali S, Brown-Borg HM, Ebadi M, Porter J (2008) Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells. Neurosci Lett 439:125–128. https://doi.org/10.1016/j.neulet.2008.05.005
Article
CAS
PubMed
PubMed Central
Google Scholar
Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) Alpha-Synuclein locus triplication causes Parkinson's disease. Science 302:841. https://doi.org/10.1126/science.1090278
Article
CAS
PubMed
Google Scholar
Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M (1998) Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A 95:6469–6473
Article
CAS
Google Scholar
Subramaniam SR, Vergnes L, Franich NR, Reue K, Chesselet MF (2014) Region specific mitochondrial impairment in mice with widespread overexpression of alpha-synuclein. Neurobiol Dis 70:204–213. https://doi.org/10.1016/j.nbd.2014.06.017
Article
CAS
PubMed
PubMed Central
Google Scholar
Surmeier DJ (2018) Determinants of dopaminergic neuron loss in Parkinson's disease. FEBS J 285:3657–3668. https://doi.org/10.1111/febs.14607
Article
CAS
PubMed
Google Scholar
Surmeier DJ, Obeso JA, Halliday GM (2017) Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 18:101–113. https://doi.org/10.1038/nrn.2016.178
Article
CAS
PubMed
PubMed Central
Google Scholar
Vicario M, Cieri D, Brini M, Cali T (2018) The close encounter between alpha-Synuclein and mitochondria. Front Neurosci 12:388. https://doi.org/10.3389/fnins.2018.00388
Article
PubMed
PubMed Central
Google Scholar
Volpicelli-Daley LA, Luk KC, Lee VM (2014) Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy neurite-like aggregates. Nat Protoc 9:2135–2146. https://doi.org/10.1038/nprot.2014.143
Article
CAS
PubMed
PubMed Central
Google Scholar
Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, Meaney DF, Trojanowski JQ, Lee VM (2011) Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72:57–71. https://doi.org/10.1016/j.neuron.2011.08.033
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang X, Wang F, Arterburn L, Wollmann R, Ma J (2006) The interaction between cytoplasmic prion protein and the hydrophobic lipid core of membrane correlates with neurotoxicity. J Biol Chem 281:13559–13565. https://doi.org/10.1074/jbc.M512306200
Article
CAS
PubMed
Google Scholar