α-Synuclein in Parkinson's disease

Cold Spring Harbor Perspectives in Medicine

Volumn 2, Issue 2, 2012, Pages

  Stefanis, Leonidas ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; BIOLOGICAL MARKER; POLYUNSATURATED FATTY ACID; SMALL INTERFERING RNA;

ALZHEIMER DISEASE; AMINO ACID METABOLISM; AMINO ACID SUBSTITUTION; ARTICLE; CELL NUCLEUS; CYTOSKELETON; DOWN REGULATION; ENDOPLASMIC RETICULUM; GENE EXPRESSION; GENE MUTATION; GENE STRUCTURE; GOLGI COMPLEX; HOMEOSTASIS; HUMAN; IMMUNOHISTOCHEMISTRY; MITOCHONDRION; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; OLIGOMERIZATION; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PHENOTYPE; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN INTERACTION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; SYNAPTIC TRANSMISSION; TRANSNEURONAL DEGENERATION; ANIMAL; CHEMISTRY; DISEASE MODEL; GENETICS; METABOLISM; PHYSIOLOGY; PROTEIN PROCESSING; REVIEW;

ALPHA-SYNUCLEIN; ANIMALS; BIOLOGICAL MARKERS; CELL NUCLEUS; CYTOSKELETON; DISEASE MODELS, ANIMAL; ENDOPLASMIC RETICULUM; GOLGI APPARATUS; HUMANS; MITOCHONDRIA; OXIDATIVE STRESS; PARKINSON DISEASE; PROTEIN MODIFICATION, TRANSLATIONAL; PROTEOLYSIS;

EID: 84866702836     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a009399     Document Type: Article

References (237)

1. Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, et al. 2000. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25: 239-252.
2. Al-Chalabi A, Dürr A, Wood NW, Parkinson MH, Camuzat A, Hulot JS, MorrisonKE, Renton A, Sussmuth SD, Landwehrmeyer BG, et al. 2009. Genetic variants of the α-synuclein gene SNCA are associated with multiple system atrophy. PLoS One 4: e7114.
3. Alim MA, Hossain MS, Arima K, Takeda K, Izumiyama Y, Nakamura M, Kaji H, Shinoda T, Hisanaga S, Ueda K. 2002. Tubulin seeds α-synuclein fibril formation. J Biol Chem 277: 2112-2117.
4. Alim MA, Ma QL, Takeda K, Aizawa T, Matsubara M, Nakamura M, Asada A, Saito T, Kaji H, Yoshii M, et al. 2004. Demonstration of a role for α-synuclein as a functional microtubule-associated protein. J Alzheimers Dis 6: 435-442.
5. Alvarez-Erviti L, Rodriguez-Oroz MC, Cooper JM, Caballero C, Ferrer I, ObesoJA, Schapira AH. 2010. Chaperone-mediated autophagy markers in Parkinson disease brains. Arch Neurol 67: 1464-1472.
6. Al-Wandi A, Ninkina N, Millership S, Williamson SJ, Jones PA, Buchman VL. 2010. Absence of α-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice. Neurobiol Aging 31: 796-804.
7. Assayag K, Yakunin E, Loeb V, Selkoe DJ, Sharon R. 2007. Polyunsaturated fatty acids induce α-synuclein-related pathogenic changes in neuronal cells. Am J Pathol 171: 2000-2011.
8. Auluck PK, Bonini NM. 2002. Pharmacological prevention of Parkinson disease in Drosophila. Nat Med 8: 1185-1186.
9. Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM. 2002. Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295: 865-868.
10. Austin SA, Floden AM, Murphy EJ, Combs CK. 2006. α-Synuclein expression modulates microglial activation phenotype. J Neurosci 26: 10558-10563.
11. Austin SA, Rojanathammanee L, Golovko MY, Murphy EJ, Combs CK. 2011. Lack of α-synuclein modulates microglial phenotype in vitro. Neurochem Res 36: 994-1004.
12. Azeredo da Silveira S, Schneider BL, Cifuentes-Diaz C, Sage D, Abbas-Terki T, Iwatsubo T, Unser M, Aebischer P. 2009. Phosphorylation does not prompt, nor prevent, the formation of α-synuclein toxic species in a rat model of Parkinson's disease. Hum Mol Genet 18: 872-887.
13. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T. 1998. Aggregation of α-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 152: 879-884.
14. Barbour R, Kling K, Anderson JP, Banducci K, Cole T, Diep L, Fox M, GoldsteinJM, Soriano F, Seubert P, et al. 2008. Red blood cells are the major source of α-synuclein in blood. Neurodegener Dis 5: 55-59.
15. Betarbet R, Canet-Aviles RM, Sherer TB, Mastroberardino PG, McLendon C, KimJH, Lund S, Na HM, Taylor G, Bence NF, et al. 2006. Intersecting pathways to neurodegeneration in Parkinson's disease: Effects of the pesticide rotenone on DJ-1, α-synuclein, and the ubiquitin-proteasome system. Neurobiol Dis 22: 404-420.
16. Bieschke J, Russ J, Friedrich RP, Ehrnhoefer DE, Wobst H, Neugebauer K, Wanker EE. 2010. EGCG remodels mature α-synuclein and amyloid-βfibrils and reduces cellular toxicity. Proc Natl Acad Sci 107: 7710-7715.
17. Bodner RA, Outeiro TF, Altmann S, Maxwell MM, Cho SH, Hyman BT, McLean PJ, Young AB, Housman DE, Kazantsev AG. 2006. Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's diseases. Proc Natl Acad Sci 103: 4246-4251.
18. Botella JA, Bayersdorfer F, Schneuwly S. 2008. Superoxide dismutase overexpression protects dopaminergic neurons in a Drosophila model of Parkinson's disease. Neurobiol Dis 30: 65-73.
19. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E. 2003. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24: 197-211.
20. Braak H, de Vos RA, Bohl J, Del Tredici K. 2006. Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett 396: 67-72.
21. Burke RE, Dauer WT, Vonsattel JP. 2008. A critical evaluation of the Braak staging scheme for Parkinson's disease. Ann Neurol 64: 485-491.
22. Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Südhof TC. 2010. α-Synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329: 1663-1667.
23. Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Chen A, Ellis CE, Paylor R, Lu B, et al. 2002. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking α-synuclein. J Neurosci 22: 8797-8807.
24. Chandra S, Gallardo G, Fernández-Chacón R, Schlüter OM, Südhof TC. 2005. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123: 383-396.
25. Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, Levecque C, Larvor L, Andrieux J, Hulihan M, et al. 2004. α-Synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364: 1167-1169.
26. Chen L, Feany MB. 2005. α-Synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci 8: 657-663.
27. Chen L, Periquet M, Wang X, Negro A, McLean PJ, Hyman BT, Feany MB. 2009. Tyrosine and serine phosphorylation of α-synuclein have opposing effects on neurotoxicity and soluble oligomer formation. J Clin Invest 119: 3257-3265.
28. Chesselet MF. 2008. In vivo α-synuclein overexpression in rodents: A useful model of Parkinson's disease? Exp Neurol 209: 22-27.
29. Chiba-Falek O, Nussbaum RL. 2001. Effect of allelic variation at the NACP-Rep1 repeat upstream of the α-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system. Hum Mol Genet 10: 3101-3109.
30. Choubey V, Safiulina D, Vaarmann A, Cagalinec M, Wareski P, Kuum M, Zharkovsky A, Kaasik A. 2011. Mutant A53T α-synuclein induces neuronal death by increasing mitochondrial autophagy. J Biol Chem 286: 10814-10824.
31. Chu Y, Kordower JH. 2007. Age-associated increases of α-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: Is this the target for Parkinson's disease? Neurobiol Dis 25: 134-149.
32. Chung CY, Koprich JB, Siddiqi H, Isacson O. 2009. Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV α-synucleinopathy. J Neurosci 29: 3365-3373.
33. Clark J, Clore EL, Zheng K, Adame A, Masliah E, Simon DK. 2010. Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in α-synuclein overexpressing mice. PLoS One 5: e12333.
34. Clough RL, Dermentzaki G, Stefanis L. 2009. Functional dissection of the α-synuclein promoter: Transcriptional regulation by ZSCAN21 and ZNF219. J Neurochem 110: 1479-1490.
35. Clough RL, Stefanis L. 2007. A novel pathway for transcriptional regulation of α-synuclein. FASEB J 21: 596-607.
36. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr. 2000. Acceleration of oligomerization, not fibrillization, is a shared property of both α-synuclein mutations linked to early-onset Parkinson's disease: Implications for pathogenesis and therapy. Proc Natl Acad Sci 97: 571-576.
37. Conway KA, Rochet JC, Bieganski RM, Lansbury PT Jr. 2001. Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct. Science 294: 1346-1349.
38. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, et al. 2006. α-Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313: 324-328.
39. Cronin KD, Ge D, Manninger P, Linnertz C, Rossoshek A, Orrison BM, BernardDJ, El-Agnaf OM, Schlossmacher MG, Nussbaum RL, et al. 2009. Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human α-synuclein in transgenic mouse brain. Hum Mol Genet 18: 3274-3285.
40. Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. 2004. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science 305: 1292-1295.
41. Cullen V, Sardi SP, Ng J, Xu YH, Sun Y, Tomlinson JJ, Kolodziej P, Kahn I, SaftigP, Woulfe J, et al. 2011. Acid β-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter α-synuclein processing. Ann Neurol 69: 940-953.
42. Dachsel JC, Lincoln SJ, Gonzalez J, Ross OA, Dickson DW, Farrer MJ. 2007. The ups and downs of α-synuclein mRNA expression. Movement Disord 22: 293-295.
43. da Costa CA, Ancolio K, Checler F. 2000. Wild-type but not Parkinson's disease-related ala-53 → Thr mutant α-synuclein protects neuronal cells from apoptotic stimuli. J Biol Chem 275: 24065-24069.
44. Danzer KM, Haasen D, Karow AR, Moussaud S, Habeck M, Giese A, Kretzschmar H, Hengerer B, Kostka M. 2007. Different species of α-synuclein oligomers induce calcium influx and seeding. J Neurosci 27: 9220-9232.
45. Danzer KM, Krebs SK, Wolff M, Birk G, Hengerer B. 2009. Seeding induced by α-synuclein oligomers provides evidence for spreading of α-synuclein pathology. J Neurochem 111: 192-203.
46. Danzer KM, Ruf WP, Putcha P, Joyner D, Hashimoto T, Glabe C, Hyman BT, McLean PJ. 2011. Heat-shock protein 70 modulates toxic extracellular α-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J 25: 326-336.
47. Darios F, Ruipérez V, López I, Villanueva J, Gutierrez LM, Davletov B. 2010. α-Synuclein sequesters arachidonic acid to modulate SNARE-mediated exocytosis. EMBO Rep 11: 528-533.
48. Dauer W, Kholodilov N, Vila M, Trillat AC, Goodchild R, Larsen KE, Staal R, TieuK, Schmitz Y, Yuan CA, et al. 2002. Resistance of α-synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci 99: 14524-14529.
49. Desplats P, Lee HJ, Bae EJ, Patrick C, Rockenstein E, Crews L, Spencer B, Masliah E, Lee SJ. 2009. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein. Proc Natl Acad Sci 106: 13010-13015.
50. Desplats P, Spencer B, Coffee E, Patel P, Michael S, Patrick C, Adame A, Rockenstein E, Masliah E. 2011. α-Synuclein sequesters Dnmt1 from the nucleus: A novel mechanism for epigenetic alterations in Lewy body diseases. J Biol Chem 286: 9031-9037.
51. Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. 2008. Mitochondrial import and accumulation of α-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem 283: 9089-9100.
52. Dickson DW, Uchikado H, Fujishiro H, Tsuboi Y. 2010. Evidence in favor of Braak staging of Parkinson's disease. Mov Disord 25 (Suppl 1): S78-S82.
53. Doxakis E. 2010. Post-transcriptional regulation of α-synuclein expression by mir-7 and mir-153. J Biol Chem 285: 12726-12734.
54. El-Agnaf OM, Salem SA, Paleologou KE, Cooper LJ, Fullwood NJ, Gibson MJ, Curran MD, Court JA, Mann DM, Ikeda S, et al. 2003. α-Synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma. FASEB J 17: 1945-1947.
55. Eliezer P, Zweckstetter D, Masliah M, Lashuel EHA. 2010. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits α-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci 30: 3184-3198.
56. Emmanoulidou E, Stefanis L, Vekrellis K. 2010a. Specific cell-derived soluble α-synuclein oligomers are degraded by the 26S proteasome and impair its function. Neurobiol Aging 31: 953-968.
57. Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, Stefanis L, Vekrellis K. 2010b. Cell-produced α-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosci 30: 6838-6851.
58. Emmanouilidiou E, Elenis D, Papasilekas T, Stranjalis G, Gerozissis K, IoannouP, Vekrellis K. 2011. In vivo assessment of α-synuclein secretion. PLoS One 6: e22225.
59. Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ, Margolis RL, Troncoso JC, Lanahan AA, Worley PF, et al. 1999. Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions. Nat Genet 22: 110-114.
60. Esposito A, Dohm CP, Kermer P, Bähr M, Wouters FS. 2007. α-Synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiol Dis 26: 521-531.
61. Feany MB, Bender WW. 2000. A Drosophila model of Parkinson's disease. Nature 404: 394-398.
62. Fortin DL, Nemani VM, Voglmaier SM, Anthony MD, Ryan TA, Edwards RH. 2005. Neural activity controls the synaptic accumulation of α-synuclein. J Neurosci 25: 10913-10921.
63. Fredenburg RA, Rospigliosi C, Meray RK, Kessler JC, Lashuel HA, Eliezer D, Lansbury PT Jr. 2007. The impact of the E46K mutation on the properties of α-synuclein in its monomeric and oligomeric states. Biochemistry 46: 7107-7118.
64. Fuchs J, Nilsson C, Kachergus J, Munz M, Larsson EM, Schüle B, Langston JW, Middleton FA, Ross OA, Hulihan M, et al. 2007. Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication. Neurology 68: 916-922.
65. Fuchs J, Tichopad A, Golub Y, Munz M, Schweitzer KJ, Wolf B, Berg D, MuellerJC, Gasser T. 2008. Genetic variability in the SNCA gene influences α-synuclein levels in the blood and brain. FASEB J 22: 1327-1334.
66. Fujita M, Sugama S, Sekiyama K, Sekigawa A, Tsukui T, Nakai M, Waragai M, Takenouchi T, Takamatsu Y, Wei J, et al. 2010. A β-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain. Nat Commun 1: 110.
67. Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, Shen J, Takio K, Iwatsubo T. 2002. α-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 4: 160-164.
68. Galvin JE, Uryu K, Lee VM, Trojanowski JQ. 1999. Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains α-, β-, and γ-synuclein. Proc Natl Acad Sci 96: 13450-13455.
69. Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ, Lee VM. 2008. Neuroinflammation and oxidation/nitration of α-synuclein linked to dopaminergic neurodegeneration. J Neurosci 28: 7687-7698.
70. Garcia-Reitböck P, Anichtchik O, Bellucci A, Iovino M, Ballini C, Fineberg E, Ghetti B, Della Corte L, Spano P, Tofaris GK, et al. 2010. SNARE protein redistribution and synaptic failure in a transgenic mouse model of Parkinson's disease. Brain 133 (Pt 7): 2032-2044.
71. George JM. 2002. The synucleins. Genome Biol 3: REVIEWS3002.
72. George JM, Jin H, Woods WS, Clayton DF. 1995. Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 15: 361-372.
73. Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, Ischiropoulos H, Trojanowski JQ, Lee VM. 2000. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 290: 985-989.
74. Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM. 2003. Initiation and synergistic fibrillization of τ and α-synuclein. Science 300: 636-640.
75. Gitler AD, Bevis BJ, Shorter J, Strathearn KE, Hamamichi S, Su LJ, Caldwell KA, Caldwell GA, Rochet JC, McCaffery JM, et al. 2008. The Parkinson's disease protein α-synuclein disrupts cellular Rab homeostasis. Proc Natl Acad Sci 105: 145-150.
76. Goers J, Manning-Bog AB, McCormack AL, Millett IS, Doniach S, Di Monte DA, Uversky VN, Fink AL. 2003. Nuclear localization of α-synuclein and its interaction with histones. Biochemistry 42: 8465-8471.
77. Gorbatyuk OS, Li S, Sullivan LF, Chen W, Kondrikova G, Manfredsson FP, Mandel RJ, Muzyczka N. 2008. The phosphorylation state of Ser-129 in human α-synuclein determines neurodegeneration in a rat model of Parkinson disease. Proc Natl Acad Sci 105: 763-768.
78. Gorbatyuk OS, Li S, Nash K, Gorbatyuk M, Lewin AS, Sullivan LF, Mandel RJ, Chen W, Meyers C, Manfredsson FP, et al. 2010. In vivo RNAi-mediated α-synuclein silencing induces nigrostriatal degeneration. Mol Ther 18: 1450-1457.
79. Gosavi N, Lee HJ, Lee JS, Patel S, Lee SJ. 2002. Golgi fragmentation occurs in the cells with prefibrillar α-synuclein aggregates and precedes the formation of fibrillar inclusion. J Biol Chem 277: 48984-48992.
80. Gründemann J, Schlaudraff F, Haeckel O, Liss B. 2008. Elevated α-synuclein mRNA levels in individual UV-laser-microdissected dopaminergic substantia nigra neurons in idiopathic Parkinson's disease. Nucleic Acids Res 36: e38.
81. Haggerty T, Credle J, Rodriguez O, Wills J, Oaks AW, Masliah E, Sidhu A. 2011. Hyperphosphorylated τ in an α-synuclein-overexpressing transgenic model of Parkinson's disease. Eur J Neurosci 33: 1598-1610.
82. Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L, Paul G, Outeiro TF, MelkiR, Kallunki P, Fog K, et al. 2011. α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest 121: 715-725.
83. Hashimoto M, Rockenstein E, Mante M, Mallory M, Masliah E. 2001. β-Synuclein inhibits α-synuclein aggregation: A possible role as an anti-parkinsonian factor. Neuron 32: 213-223.
84. 2+ signaling in human neuroblastoma (SH-SY5Y) cells. J Neurochem 111: 1192-1201.
85. Hodara R, Norris EH, Giasson BI, Mishizen-Eberz AJ, Lynch DR, Lee VM, Ischiropoulos H. 2004. Functional consequences of α-synuclein tyrosine nitration: Diminished binding to lipid vesicles and increased fibril formation. J Biol Chem 279: 47746-47753.
86. Hong Z, Shi M, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Leverenz JB, Baird G, et al. 2010. DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain 133 (Pt 3): 713-726.
87. Hsu LJ, Sagara Y, Arroyo A, Rockenstein E, Sisk A, Mallory M, Wong J, Takenouchi T, Hashimoto M, Masliah E. 2000. α-Synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol 157: 401-410.
88. Inglis KJ, Chereau D, Brigham EF, Chiou SS, Schöbel S, Frigon NL, Yu M, Caccavello RJ, Nelson S, Motter R, et al. 2009. Polo-like kinase 2 (PLK2) phosphorylates α-synuclein at serine 129 in central nervous system. J Biol Chem 284: 2598-2602.
89. Jensen PH, Hager H, Nielsen MS, Hojrup P, Gliemann J, Jakes R. 1999. α-Synuclein binds to τ and stimulates the protein kinase A-catalyzed τphosphorylation of serine residues 262 and 356. J Biol Chem 274: 25481-25489.
90. Jin H, Kanthasamy A, Ghosh A, Yang Y, Anantharam V, Kanthasamy AG. 2011. α-Synuclein negatively regulates protein kinase Cδ expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity. J Neurosci 31: 2035-2051.
91. Jowaed A, Schmitt I, Kaut O, Wüllner U. 2010. Methylation regulates α-synuclein expression and is decreased in Parkinson's disease patients' brains. J Neurosci 30: 6355-6359.
92. Junn E, Lee KW, Jeong BS, Chan TW, Im JY, Mouradian MM. 2009. Repression of α-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci 106: 13052-13057.
93. Kahle PJ. 2008. α-Synucleinopathy models and human neuropathology: Similarities and differences. Acta Neuropathol 115: 87-95.
94. Kamp F, Exner N, Lutz AK, Wender N, Hegermann J, Brunner B, Nuscher B, Bartels T, Giese A, Beyer K, et al. 2010. Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J 29: 3571-3589.
95. Karpinar DP, Balija MB, Kügler S, Opazo F, Rezaei-Ghaleh N, Wender N, Kim HY, Taschenberger G, Falkenburger BH, Heise H, et al. 2009. Pre-fibrillar α-synuclein variants with impaired β-structure increase neurotoxicity in Parkinson's disease models. EMBO J 28: 3256-3268.
96. Kasuga K, Tokutake T, Ishikawa A, Uchiyama T, Tokuda T, Onodera O, Nishizawa M, Ikeuchi T. 2010. Differential levels of α-synuclein, β-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease. J Neurol Neurosurg Psychiatry 81: 608-610.
97. Kholodilov NG, Neystat M, Oo TF, Lo SE, Larsen KE, Sulzer D, Burke RE. 1999. Increased expression of rat synuclein in the substantia nigra pars compacta identified by mRNA differential display in a model of developmental target injury. J Neurochem 73: 2586-2599.
98. Kim TD, Paik SR, Yang CH. 2002. Structural and functional implications of C-terminal regions of α-synuclein. Biochemistry 41: 13782-13790.
99. Kirik D, Rosenblad C, Burger C, Lundberg C, Johansen TE, Muzyczka N, MandelRJ, Bjorklund A. 2002. Parkinson-like neurodegeneration induced by targeted overexpression of α-synuclein in the nigrostriatal system. J Neurosci 22: 2780-2791.
100. Klegeris A, Pelech S, Giasson BI, Maguire J, Zhang H, McGeer EG, McGeer PL. 2008. α-Synuclein activates stress signaling protein kinases in THP-1 cells and microglia. Neurobiol Aging 29: 739-752.
101. Klucken J, Shin Y, Masliah E, Hyman BT, McLean PJ. 2004. Hsp70 reduces α-synuclein aggregation and toxicity. J Biol Chem 279: 25497-25502.
102. Kobayashi H, Krüger R, Markopoulou K, Wszolek Z, Chase B, Taka H, Mineki R, Murayama K, Riess O, Mizuno Y, et al. 2003. Haploinsufficiency at the α-synuclein gene underlies phenotypic severity in familial Parkinson's disease. Brain 126 (Pt 1): 32-42.
103. Kontopoulos E, Parvin JD, Feany MB. 2006. α-Synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 15: 3012-3023.
104. Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. 2008. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 14: 504-506.
105. Kostka M, Högen T, Danzer KM, Levin J, Habeck M, Wirth A, Wagner R, GlabeCG, Finger S, Heinzelmann U, et al. 2008. Single particle characterization of iron-induced pore-forming α-synuclein oligomers. J Biol Chem 283: 10992-11003.
106. Kotzbauer PT, Giasson BI, Kravitz AV, Golbe LI, Mark MH, Trojanowski JQ, LeeVM. 2004. Fibrillization of α-synuclein and tau in familial Parkinson's disease caused by the A53T α-synuclein mutation. Exp Neurol 187: 279-288.
107. Kramer ML, Schulz-Schaeffer WJ. 2007. Presynaptic α-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci 27: 1405-1410.
108. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, EpplenJT, Schols L, Riess O. 1998. Ala30Pro mutation in the gene encoding α-synuclein in Parkinson's disease. Nat Genet 18: 106-108.
109. Kuo YM, Li Z, Jiao Y, Gaborit N, Pani AK, Orrison BM, Bruneau BG, Giasson BI, Smeyne RJ, Gershon MD, et al. 2010. Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated α-synuclein gene mutations precede central nervous system changes. Hum Mol Genet 19: 1633-1650.
110. Lakso M, Vartiainen S, Moilanen AM, Sirvio J, Thomas JH, Nass R, Blakely RD, Wong G. 2003. Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. J Neurochem 86: 165-172.
111. Larsen KE, Schmitz Y, Troyer M, Mosharov E, Dietrich P, Savalle M, Quazi AZ, Chaudhry FA, Edwards R, Stefanis L, et al. 2006. α-Synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci 26: 11915-11922.
112. Lee HJ, Shin SY, Choi C, Lee YH, Lee SJ. 2002. Formation and removal of α-synuclein aggregates in cells exposed to mitochondrial inhibitors. J Biol Chem 277: 5411-5417.
113. Lee HJ, Khoshaghideh F, Patel S, Lee SJ. 2004. Clearance of α-synuclein oligomeric intermediates via the lysosomal degradation pathway. J Neurosci 24: 1888-1896.
114. Lee HJ, Patel S, Lee SJ. 2005. Intravesicular localization and exocytosis of α-synuclein and its aggregates. J Neurosci 25: 6016-6024.
115. Lee HJ, Khoshaghideh F, Lee S, Lee SJ. 2006. Impairment of microtubule-dependent trafficking by overexpression of α-synuclein. Eur J Neurosci 24: 3153-3162.
116. Lee HJ, Suk JE, Patrick C, Bae EJ, Cho JH, Rho S, Hwang D, Masliah E, Lee SJ. 2010. Direct transfer of α-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 285: 9262-9272.
117. Lee KW, Chen W, Junn E, Im JY, Grosso H, Sonsalla PK, Feng X, Ray N, Fernandez JR, Chao Y, et al. 2011. Enhanced phosphatase activity attenuates α-synucleinopathy in a mouse model. J Neurosci 31: 6963-6971.
118. Leong SL, Pham CL, Galatis D, Fodero-Tavoletti MT, Perez K, Hill AF, MastersCL, Ali FE, Barnham KJ, Cappai R. 2009. Formation of dopamine-mediated α-synuclein-soluble oligomers requires methionine oxidation. Free Radical Bio Med 46: 1328-1337.
119. Li W, West N, Colla E, Pletnikova O, Troncoso JC, Marsh L, Dawson TM, JäkäläP, Hartmann T, Price DL, et al. 2005. Aggregation promoting C-terminal truncation of α-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations. Proc Natl Acad Sci 102: 2162-2167.
120. Li WW, Yang R, Guo JC, Ren HM, Zha XL, Cheng JS, Cai DF. 2007. Localization of α-synuclein to mitochondria within midbrain of mice. Neuroreport 18: 1543-1546.
121. Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L, Xie C, Long CX, Yang WJ, Ding J, et al. 2009. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant α-synuclein. Neuron 64: 807-827.
122. Lindersson E, Beedholm R, Højrup P, Moos T, Gai W, Hendil KB, Jensen PH. 2004. Proteasomal inhibition by alpha-synuclein filaments and oligomers. J Biol Chem 279: 12924-12934.
123. Linnertz C, Saucier L, Ge D, Cronin KD, Burke JR, Browndyke JN, Hulette CM, Welsh-Bohmer KA, Chiba-Falek O. 2009. Genetic regulation of α-synuclein mRNA expression in various human brain tissues. PLoS One 4: e7480.
124. Liu F, Nguyen JL, Hulleman JD, Li L, Rochet JC. 2008. Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson's disease. J Neurochem 105: 2435-2453.
125. Liu G, Zhang C, Yin J, Li X, Cheng F, Li Y, Yang H, Uéda K, Chan P, Yu S. 2009. α-Synuclein is differentially expressed in mitochondria from different rat brain regions and dose-dependently down-regulates complex I activity. Neurosci Lett 454: 187-192.
126. Liu Z, Yu Y, Li X, Ross CA, Smith WW. 2011. Curcumin protects against A53T α-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacol Res 63: 439-444.
127. Lo Bianco C, Ridet JL, Schneider BL, Deglon N, Aebischer P. 2002. α-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc Natl Acad Sci 99: 10813-10818.
128. Loeb V, Yakunin E, Saada A, Sharon R. 2010. The transgenic overexpression of α-synuclein and not its related pathology associates with complex I inhibition. J Biol Chem 285: 7334-7343.
129. Luk KC, Song C, O'Brien P, Stieber A, Branch JR, Brunden KR, Trojanowski JQ, Lee VM. 2009. Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci 106: 20051-20056.
130. Mak SK, McCormack AL, Manning-Bog AB, Cuervo AM, Di Monte DA. 2010. Lysosomal degradation of α-synuclein in vivo. J Biol Chem 285: 13621-13629.
131. Manning-Boǧ AB, Schüle B, Langston JW. 2009. α-Synuclein-glucocerebrosidase interactions in pharmacological Gaucher models: A biological link between Gaucher disease and parkinsonism. Neurotoxicology 30: 1127-1132.
132. Maraganore DM, de Andrade M, Elbaz A, Farrer MJ, Ioannidis JP, Kruger R, Rocca WA, Schneider NK, Lesnick TG, Lincoln SJ, et al. 2006. (GEO-PD) Consortium. Collaborative analysis of α-synuclein gene promoter variability and Parkinson disease. JAMA 296: 661-670.
133. Markopoulou K, Wszolek ZK, Pfeiffer RF, Chase BA. 1999. Reduced expression of the G209A α-synuclein allele in familial Parkinsonism. Ann Neurol 46: 374-381.
134. Maroteaux L, Scheller RH. 1991. The rat brain synucleins; family of proteins transiently associated with neuronal membrane. Brain Res Mol Brain Res 11: 335-343.
135. Maroteaux L, Campanelli JT, Scheller RH. 1988. Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8: 2804-2815.
136. Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA, Price DL, LeeMK. 2006. Parkinson's disease α-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci 26: 41-50.
137. Martìn-Clemente B, Alvarez-Castelao B, Mayo I, Sierra AB, Dìaz V, Milán M, Fariñas I, Gómez-Isla T, Ferrer I, Castaño JG. 2004. α-Synuclein expression levels do not significantly affect proteasome function and expression in mice and stably transfected PC12 cell lines. J Biol Chem 279: 52984-52990.
138. Martinez-Vicente M, Talloczy Z, Kaushik S, Massey AC, Mazzulli J, MosharovEV, Hodara R, Fredenburg R, Wu DC, Follenzi A, et al. 2008. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 118: 777-788.
139. Masliah E, Rockenstein E, Adame A, Alford M, Crews L, Hashimoto M, SeubertP, Lee M, Goldstein J, Chilcote T, et al. 2005. Effects of α-synuclein immunization in a mouse model of Parkinson's disease. Neuron 46: 857-868.
140. Masliah E, Rockenstein E, Mante M, Crews L, Spencer B, Adame A, Patrick C, Trejo M, Ubhi K, Rohn TT, et al. 2011. Passive immunization reduces behavioral and neuropathological deficits in an α-synuclein transgenic model of Lewy body disease. PLoS One 6: e19338.
141. Mata IF, Shi M, Agarwal P, Chung KA, Edwards KL, Factor SA, Galasko DR, Ginghina C, Griffith A, Higgins DS, et al. 2010. SNCA variant associated with Parkinson disease and plasma α-synuclein level. Arch Neurol 67: 1350-1356.
142. Matsumoto L, Takuma H, Tamaoka A, Kurisaki H, Date H, Tsuji S, Iwata A. 2010. CpG demethylation enhances α-synuclein expression and affects the pathogenesis of Parkinson's disease. PLoS One 5: e15522.
143. Mazzulli JR, Mishizen AJ, Giasson BI, Lynch DR, Thomas SA, Nakashima A, Nagatsu T, Ota A, Ischiropoulos H. 2006. Cytosolic catechols inhibit α-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates. J Neurosci 26: 10068-10078.
144. Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. 2011. Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell 146: 37-52.
145. Mbefo MK, Paleologou KE, Boucharaba A, Oueslati A, Schell H, Fournier M, Olschewski D, Yin G, Zweckstetter M, Masliah E, et al. 2010. Phosphorylation of synucleins by members of the Polo-like kinase family. J Biol Chem 285: 2807-2822.
146. McCarthy JJ, Linnertz C, Saucier L, Burke JR, Hulette CM, Welsh-Bohmer KA, Chiba-Falek O. 2011. The effect of SNCA 3′ region on the levels of SNCA-112 splicing variant. Neurogenetics 12: 59-64.
147. McCormack AL, Mak SK, Henderson JM, Bumcrot D, Farrer MJ, Di Monte DA. 2010. α-Synuclein suppression by targeted small interfering RNA in the primate substantia nigra. PLoS One 5: e12122.
148. Miller DW, Hague SM, Clarimon J, Baptista M, Gwinn-Hardy K, Cookson MR, Singleton AB. 2004. α-Synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology 62: 1835-1838.
149. Mirzaei H, Schieler JL, Rochet JC, Regnier F. 2006. Identification of rotenone-induced modifications in α-synuclein using affinity pull-down and tandem mass spectrometry. Anal Chem 78: 2422-2431.
150. Mishizen-Eberz AJ, Guttmann RP, Giasson BI, Day GA, Hodara R, IschiropoulosH, Lee VM, Trojanowski JQ, Lynch DR. 2003. Distinct cleavage patterns of normal and pathologic forms of α-synuclein by calpain I in vitro. J Neurochem 86: 836-847.
151. Mishizen-Eberz AJ, Norris EH, Giasson BI, Hodara R, Ischiropoulos H, Lee VM, Trojanowski JQ, Lynch DR. 2005. Cleavage of α-synuclein by calpain: Potential role in degradation of fibrillized and nitrated species of α-synuclein. Biochemistry 44: 7818-7829.
152. Mizuta I, Satake W, Nakabayashi Y, Ito C, Suzuki S, Momose Y, Nagai Y, Oka A, Inoko H, Fukae J, et al. 2006. Multiple candidate gene analysis identifies α-synuclein as a susceptibility gene for sporadic Parkinson's disease. Hum Mol Genet 15: 1151-1158.
153. Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I, Ng J, Schulz-Schaeffer W, Kretzschmar HA, McLean PJ, et al. 2008. Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 213: 315-325.
154. Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, Sixel-Döring F, TrenkwalderC, Schlossmacher MG. 2011. α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: A cohort study. Lancet Neurol 10: 230-240.
155. Mori F, Tanji K, Yoshimoto M, Takahashi H, Wakabayashi K. 2002a. Demonstration of α-synuclein immunoreactivity in neuronal and glial cytoplasm in normal human brain tissue using proteinase K and formic acid pretreatment. Exp Neurol 176: 98-104.
156. Mori F, Tanji K, Yoshimoto M, Takahashi H, Wakabayashi K. 2002b. Immunohistochemical comparison of α-and β-synuclein in adult rat central nervous system. Brain Res 941: 118-126.
157. Mosharov EV, Staal RG, Bové J, Prou D, Hananiya A, Markov D, Poulsen N, Larsen KE, Moore CM, Troyer MD, et al. 2006. α-Synuclein overexpression increases cytosolic catecholamine concentration. J Neurosci 26: 9304-9311.
158. Mosharov EV, Larsen KE, Kanter E, Phillips KA, Wilson K, Schmitz Y, Krantz DE, Kobayashi K, Edwards RH, Sulzer D. 2009. Interplay between cytosolic dopamine, calcium, and α-synuclein causes selective death of substantia nigra neurons. Neuron 62: 218-229.
159. Mosley RL, Hutter-Saunders JA, Stone DK, Gendelman HE. 2012. Inflammation and adaptive immunity in Parkinson's disease. Cold Spring Harb Perspect Med (in press).
160. Mueller JC, Fuchs J, Hofer A, Zimprich A, Lichtner P, Illig T, Berg D, Wüllner U, Meitinger T, Gasser T. 2005. Multiple regions of α-synuclein are associated with Parkinson's disease. Ann Neurol 57: 535-541.
161. Murphy DD, Rueter SM, Trojanowski JQ, Lee VM. 2000. Synucleins are developmentally expressed, and α-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J Neurosci 20: 3214-3220.
162. Murray IV, Giasson BI, Quinn SM, Koppaka V, Axelsen PH, Ischiropoulos H, Trojanowski JQ, Lee VM. 2003. Role of α-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry 42: 8530-8540.
163. Nakamura K, Nemani VM, Wallender EK, Kaehlcke K, Ott M, Edwards RH. 2008. Optical reporters for the conformation of alpha-synuclein reveal a specific interaction with mitochondria. J Neurosci 28: 12305-12317.
164. Nakamura K, Nemani VM, Azarbal F, Skibinski G, Levy JM, Egami K, Munishkina L, Zhang J, Gardner B, Wakabayashi J, et al. 2011. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein α-synuclein. J Biol Chem 286: 20710-20726.
165. Nakayama K, Suzuki Y, Yazawa I. 2009. Microtubule depolymerization suppresses α-synuclein accumulation in a mouse model of multiple system atrophy. Am J Pathol 174: 1471-1480.
166. Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón-Sánchez J, Schulte C, Lesage S, Sveinbjörnsdóttir S, et al. 2011. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: A meta-analysis of genome-wide association studies. Lancet 377: 641-649.
167. Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, NicollRA, Edwards RH. 2010. Increased expression of α-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65: 66-79.
168. Nonaka T, Watanabe ST, Iwatsubo T, Hasegawa M. 2010. Seeded aggregation and toxicity of α-synuclein and tau: Cellular models of neurodegenerative diseases. J Biol Chem 285: 34885-34898.
169. Ohtake H, Limprasert P, Fan Y, Onodera O, Kakita A, Takahashi H, Bonner LT, Tsuang DW, Murray IV, Lee VM, et al. 2004. β-Synuclein gene alterations in dementia with Lewy bodies. Neurology 63: 805-811.
170. Ostrerova N, Petrucelli L, Farrer M, Mehta N, Choi P, Hardy J, Wolozin B. 1999. α-Synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci 19: 5782-5791.
171. Ostrerova-Golts N, Petrucelli L, Hardy J, Lee JM, Farer M, Wolozin B. 2000. The A53T α-synuclein mutation increases iron-dependent aggregation and toxicity. J Neurosci 20: 6048-6054.
172. Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, et al. 2007. Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson's disease. Science 317: 516-519.
173. Paillusson S, Tasselli M, Lebouvier T, Mahé M, Chevalier J, Biraud M, Cario-Toumaniantz C, Neunlist M, Derkinderen P. 2010. α-Synuclein expression is induced by depolarization and cyclic AMP in enteric neurons. J Neurochem 115: 694-706.
174. Paleologou KE, Schmid AW, Rospigliosi CC, Kim HY, Lamberto GR, FredenburgRA, Lansbury PT, Fernandez CO, Eliezer D, Zweckstetter M, et al. 2008. Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of α-synuclein. J Biol Chem 283: 16895-16905.
175. Paleologou KE, Kragh CL, Mann DM, Salem SA, Al-Shami R, Allsop D, HassanAH, Jensen PH, El-Agnaf OM. 2009. Detection of elevated levels of soluble α-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies. Brain 132 (Pt 4): 1093-1101.
176. Paleologou KE, Oueslati A, Shakked G, Rospigliosi CC, Kim HY, Lamberto GR, Fernandez CO, Schmid A, Chegini F, Gai WP, et al. 2010. Phsophorylation at S87 is enhanced in synucleinopathies, nhibits α-synuclein oligomerization and influences synuclein-membrane interactions. J Neurosci 30: 3184-3198.
177. Pan-Montojo F, Anichtchik O, Dening Y, Knels L, Pursche S, Jung R, Jackson S, Gille G, Spillantini MG, Reichmann H, et al. 2010. Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 5: e8762.
178. Park JY, Lansbury PT Jr. 2003. β-Synuclein inhibits formation of α-synuclein protofibrils: A possible therapeutic strategy against Parkinson's disease. Biochemistry 42: 3696-3700.
179. Paxinou E, Chen Q, Weisse M, Giasson BI, Norris EH, Rueter SM, TrojanowskiJQ, Lee VM, Ischiropoulos H. 2001. Induction of α-synuclein aggregation by intracellular nitrative insult. J Neurosci 21: 8053-8061.
180. Peng XM, Tehranian R, Dietrich P, Stefanis L, Perez R. 2005. α-Synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. J Cell Sci 118 (Pt 15): 3523-3530.
181. Perez RG, Waymire JC, Lin E, Liu JJ, Guo F, Zigmond MJ. 2002. A role for α-synuclein in the regulation of dopamine biosynthesis. J Neurosci 22: 3090-3099.
182. Periquet M, Fulga T, Myllykangas L, Schlossmacher MG, Feany MB. 2007. Aggregated α-synuclein mediates dopaminergic neurotoxicity in vivo. J Neurosci 27: 3338-3346.
183. Perrin RJ, Woods WS, Clayton DF, George JM. 2001. Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J Biol Chem 276: 41958-41962.
184. Petrucelli L, O'Farrell C, Lockhart PJ, Baptista M, Kehoe K, Vink L, Choi P, Wolozin B, Farrer M, Hardy J, et al. 2002. Parkin protects against the toxicity associated with mutant α-synuclein: Proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36: 1007-1019.
185. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, et al. 1997. Mutation in the α-synuclein gene identified in families with Parkinson's disease. Science 276: 2045-2047.
186. Qin Z, Hu D, Han S, Reaney SH, Di Monte DA, Fink AL. 2007. Effect of 4-hydroxy-2-nonenal modification on α-synuclein aggregation. J Biol Chem 282: 5862-5870.
187. Qureshi HY, Paudel HK. 2011. Parkinsonian neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and α-synuclein mutations promote τprotein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro. J Biol Chem 286: 5055-5068.
188. Rideout HJ, Dietrich P, Savalle M, Dauer WT, Stefanis L. 2003. Regulation of α-synuclein by bFGF in cultured ventral midbrain dopaminergic neurons. J Neurochem 84: 803-813.
189. Rideout HJ, Dietrich P, Wang QH, Dauer WT, Stefanis L. 2004. α-Synuclein is required for the fibrillar nature of ubiquitinated inclusions induced by proteasomal inhibition in primary neurons. J Biol Chem 279: 46915-46920.
190. Robertson DC, Schmidt O, Ninkina N, Jones PA, Sharkey J, Buchman VL. 2004. Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of γ-synuclein, α-synuclein and double α/γ-synuclein null mutant mice. J Neurochem 89: 1126-1136.
191. Schell H, Hasegawa T, Neumann M, Kahle PJ. 2009. Nuclear and neritic distribution of serine-129 phosphorylated α-synuclein in transgenic mice. Neuroscience 160: 796-804.
192. Scherzer CR, Grass JA, Liao Z, Pepivani I, Zheng B, Eklund AC, Ney PA, Ng J, McGoldrick M, Mollenhauer B, et al. 2008. GATA transcription factors directly regulate the Parkinson's disease-linked gene α-synuclein. Proc Natl Acad Sci 105: 10907-10912.
193. Scholz SW, Houlden H, Schulte C, Sharma M, Li A, Berg D, Melchers A, PaudelR, Gibbs JR, Simon-Sanchez J, et al. 2009. SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol 65: 610-614.
194. Scott DA, Tabarean I, Tang Y, Cartier A, Masliah E, Roy S. 2010. A pathologic cascade leading to synaptic dysfunction in α-synuclein-induced neurodegeneration. J Neurosci 30: 8083-8095.
195. Sharon R, Bar-Joseph I, Frosch MP, Walsh DM, Hamilton JA, Selkoe DJ. 2003. The formation of highly soluble oligomers of α-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 37: 583-595.
196. Shimshek DR, Mueller M, Wiessner C, Schweizer T, van der Putten PH. 2010. The HSP70 molecular chaperone is not beneficial in a mouse model of α-synucleinopathy. PLoS One 5: e10014.
197. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, HulihanM, Peuralinna T, Dutra A, Nussbaum R, et al. 2003. α-Synuclein locus triplication causes Parkinson's disease. Science 302: 841.
198. Smith WW, Jiang H, Pei Z, Tanaka Y, Morita H, Sawa A, Dawson VL, DawsonTM, Ross CA. 2005. Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity. Hum Mol Genet 14: 3801-3811.
199. Smith WW, Liu Z, Liang Y, Masuda N, Swing DA, Jenkins NA, Copeland NG, Troncoso JC, Pletnikov M, Dawson TM, et al. 2010. Synphilin-1 attenuates neuronal degeneration in the A53T α-synuclein transgenic mouse model. Hum Mol Genet 19: 2087-2098.
200. Snyder H, Mensah K, Theisler C, Lee J, Matouschek A, Wolozin B. 2003. Aggregated and monomeric α-synuclein bind to the S6' proteasomal protein and inhibit proteasomal function. J Biol Chem 278: 11753-11759.
201. Sousa VL, Bellani S, Giannandrea M, Yousuf M, Valtorta F, Meldolesi J, Chieregatti E. 2009. α-Synuclein and its A30P mutant affect actin cytoskeletal structure and dynamics. Mol Biol Cell 20: 3725-3739.
202. Spencer B, Potkar R, Trejo M, Rockenstein E, Patrick C, Gindi R, Adame A, Wyss-Coray T, Masliah E. 2009. Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in α-synuclein models of Parkinson's and Lewy body diseases. J Neurosci 29: 13578-13588.
203. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. 1997. α-Synuclein in Lewy bodies. Nature 388: 839-840.
204. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. 1998. α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci 95: 6469-6473.
205. Stefanis L, Larsen KE, Rideout HJ, Sulzer D, Greene LA. 2001. Expression of A53T mutant but not wild-type α-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J Neurosci 21: 9549-9560.
206. Stefanis L, Wang Q, Oo T, Lang-Rollin I, Burke RE, Dauer WT. 2004. Lack of α-synuclein does not alter apoptosis of neonatal catecholaminergic neurons. Eur J Neurosci 20: 1969-1972.
207. Tanaka Y, Engelender S, Igarashi S, Rao RK, Wanner T, Tanzi RE, Sawa A, Dawson V, Dawson TM, Ross CA. 2001. Inducible expression of mutant α-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum Mol Genet 10: 919-926.
208. Thayanidhi N, Helm JR, Nycz DC, Bentely M, Liang Y, Hay JC. 2010. α-Synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell 21: 1850-1863.
209. Tofaris GK, Layfield R, Spillantini MG. 2001. alpha-synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome. FEBS Lett 509: 22-26.
210. Tokuda T, Salem SA, Allsop D, Mizuno T, Nakagawa M, Qureshi MM, LocascioJJ, Schlossmacher MG, El-Agnaf OM. 2006. Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease. Biochem Biophys Res Commun 349: 162-166.
211. Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T, Ishigami N, Tamaoka A, Nakagawa M, El-Agnaf OM. 2010. Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75: 1766-1772.
212. Tong J, Wong H, Guttman M, Ang LC, Forno LS, Shimadzu M, Rajput AH, Muenter MD, Kish SJ, Hornykiewicz O, et al. 2010. Brain α-synuclein accumulation in multiple system atrophy, Parkinson's disease and progressive supranuclear palsy: A comparative investigation. Brain 133 (Pt 1): 172-188.
213. Tsika E, Moysidou M, Guo J, Cushman M, Gannon P, Sandaltzopoulos R, Giasson BI, Krainc D, Ischiropoulos H, Mazzulli JR. 2010. Distinct region-specific α-synuclein oligomers in A53T transgenic mice: Implications for neurodegeneration. J Neurosci 30: 3409-3418.
214. Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, KondoJ, Ihara Y, Saitoh T. 1993. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci 90: 11282-11286.
215. Uversky VN, Yamin G, Munishkina LA, Karymov MA, Millett IS, Doniach S, Lyubchenko YL, Fink AL. 2005. Effects of nitration on the structure and aggregation of α-synuclein. Brain Res Mol Brain Res 134: 84-102.
216. Vekrellis K, Xilouri M, Emmanouilidou E, Stefanis L. 2009. Inducible over-expression of wild type α-synuclein in human neuronal cells leads to caspase-dependent non-apoptotic death. J Neurochem 109: 1348-1362.
217. Vila M, Vukosavic S, Jackson-Lewis V, Neystat M, Jakowec M, Przedborski S. 2000. α-Synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP. J Neurochem 74: 721-729.
218. Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L. 2008. Wild type α-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem 283: 23542-23556.
219. Volles MJ, Lansbury PT Jr. 2002. Vesicle permeabilization by protofibrillar α-synuclein is sensitive to Parkinson's disease-linked mutations and occurs by a pore-like mechanism. Biochemistry 41: 4595-4602.
220. Voutsinas GE, Stavrou EF, Karousos G, Dasoula A, Papachatzopoulou A, SyrrouM, Verkerk AJ, van der Spek P, Patrinos GP, Stöger R, et al. 2010. Allelic imbalance of expression and epigenetic regulation within the α-synuclein wild-type and p. Ala53Thr alleles in Parkinson disease. Hum Mutat 31: 685-691.
221. Wassef R, Haenold R, Hansel A, Brot N, Heinemann SH, Hoshi T. 2007. Methionine sulfoxide reductase A and a dietary supplement S-methyl-L-cysteine prevent Parkinson's-like symptoms. J Neurosci 27: 12808-12816.
222. Waxman EA, Giasson BI. 2010. A novel, high-efficiency cellular model of fibrillar α-synuclein inclusions and the examination of mutations that inhibit amyloid formation. J Neurochem 113: 374-388.
223. Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC. 2003. α-Synuclein is degraded by both autophagy and the proteasome. J Biol Chem 278: 25009-25013.
224. Wersinger C, Sidhu A. 2003. Attenuation of dopamine transporter activity by α-synuclein. Neurosci Lett 340: 189-192.
225. Wersinger C, Prou D, Vernier P, Sidhu A. 2003. Modulation of dopamine transporter function by α-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. FASEB J 17: 2151-2153.
226. Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. 2003. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein. Science 302: 1769-1772.
227. Winner B, Jappelli R, Maji SK, Desplats PA, Boyer L, Aigner S, Hetzer C, Loher T, Vilar M, Campioni S, et al. 2011. In vivo demonstration that α-synuclein oligomers are toxic. Proc Natl Acad Sci 108: 4194-4199.
228. Winslow AR, Chen CW, Corrochano S, Acevedo-Arozena A, Gordon DE, PedenAA, Lichtenberg M, Menzies FM, Ravikumar B, Imarisio S, et al. 2010. α-Synuclein impairs macroautophagy: Implications for Parkinson's disease. J Cell Biol 190: 1023-1037.
229. Withers GS, George JM, Banker GA, Clayton DF. 1997. Delayed localization of synelfin (synuclein, NACP) to presynaptic terminals in cultured rat hippocampal neurons. Brain Res Dev Brain Res 99: 87-94.
230. Xilouri M, Vogiatzi T, Vekrellis K, Stefanis L. 2008. α-Synuclein degradation by autophagic pathways: A potential key to Parkinson's disease pathogenesis. Autophagy 4: 917-919.
231. Xilouri M, Vogiatzi T, Vekrellis K, Park D, Stefanis L. 2009. Abberant α-synuclein confers toxicity to neurons in part through inhibition of chaperone-mediated autophagy. PLoS One 4: e5515.
232. Xu YH, Sun Y, Ran H, Quinn B, Witte D, Grabowski GA. 2011. Accumulation and distribution of α-synuclein and ubiquitin in the CNS of Gaucher disease mouse models. Mol Genet Metab 102: 436-447.
233. Yu S, Li X, Liu G, Han J, Zhang C, Li Y, Xu S, Liu C, Gao Y, Yang H, et al. 2007. Extensive nuclear localization of α-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience 145: 539-555.
234. Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atarés B, et al. 2004. The new mutation, E46K, of α-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55: 164-173.
235. Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhang W, Zhou Y, Hong JS, et al. 2005. Aggregated α-synuclein activates microglia: A process leading to disease progression in Parkinson's disease. FASEB J 19: 533-542.
236. Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, et al. 2010. PGC-1α, a potential therapeutic target for early intervention in Parkinson's disease. Sci Transl Med 2: 52ra73.
237. Zhou RM, Huang YX, Li XL, Chen C, Shi Q, Wang GR, Tian C, Wang ZY, Jing YY, Gao C, et al. 2010. Molecular interaction of α-synuclein with tubulin influences on the polymerization of microtubule in vitro and structure of microtubule in cells. Mol Biol Rep 37: 3183-3192.