α-Synuclein and nonhuman primate models of Parkinson's disease

Journal of Neuroscience Methods

Volumn 255, Issue , 2015, Pages 38-51

  Vermilyea, Scott C ^a,b   Emborg, Marina E ^a,b,c  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF WISCONSIN   (United States)

^c UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Alpha synuclein; Animal models; Lewy body; Lewy neurite; Nonhuman primates; Parkinson's disease

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; ALPHA SYNUCLEIN; NEUROTOXIN; OXIDOPAMINE; VIRUS VECTOR;

AGING; AMINO ACID SEQUENCE; GENE TARGETING; GENE TRANSFER; HUMAN; INOCULATION; LEWY BODY; NEURITE; NONHUMAN; PARKINSON DISEASE; PRIMATE MODEL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; REVIEW; TRANSGENICS; ANIMAL; BRAIN; GENETICS; METABOLISM; PARKINSONISM; PATHOLOGY; PRIMATE;

ALPHA-SYNUCLEIN; ANIMALS; BRAIN; HUMANS; PARKINSONIAN DISORDERS; PRIMATES;

EID: 84939641927     PISSN: 01650270     EISSN: 1872678X     Source Type: Journal    
DOI: 10.1016/j.jneumeth.2015.07.025     Document Type: Review

References (118)

1. Alvarez-Fischer D., Henze C., Strenzke C., Westrich J., Ferger B., Hoglinger G.U., et al. Characterization of the striatal 6-OHDA model of Parkinson's disease in wild type and alpha-synuclein-deleted mice. Exp Neurol 2008, 210:182-193.
2. Bartels T., Choi J.G., Selkoe D.J. alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 2011, 477:107-110.
3. Bendor J.T., Logan T.P., Edwards R.H. The function of alpha-synuclein. Neuron 2013, 79:1044-1066.
4. Betarbet R., Sherer T.B., MacKenzie G., Garcia-Osuna M., Panov A.V., Greenamyre J.T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci 2000, 3:1301-1306.
5. Bjorklund A., Kirik D., Rosenblad C., Georgievska B., Lundberg C., Mandel R.J. Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res 2000, 886:82-98.
6. Blandini F., Armentero M.T., Martignoni E. The 6-hydroxydopamine model: news from the past. Parkinsonism Relat Disord 2008, 14(Suppl. 2):S124-S129.
7. Blum D., Torch S., Lambeng N., Nissou M., Benabid A.L., Sadoul R., et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol 2001, 65:135-172.
8. Bove J., Zhou C., Jackson-Lewis V., Taylor J., Chu Y., Rideout H.J., et al. Proteasome inhibition and Parkinson's disease modeling. Ann Neurol 2006, 60:260-264.
9. Braak H., Braak E., Yilmazer D., Schultz C., de Vos R.A., Jansen E.N. Nigral and extranigral pathology in Parkinson's disease. J Neural Transm Suppl 1995, 46:15-31.
10. Braak H., Ghebremedhin E., Rub U., Bratzke H., Del Tredici K. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res 2004, 318:121-134.
11. Burger C., Gorbatyuk O.S., Velardo M.J., Peden C.S., Williams P., Zolotukhin S., et al. Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther 2004, 10:302-317.
12. Canron M.H., Perret M., Vital A., Bezard E., Dehay B. Age-dependent alpha-synuclein aggregation in the Microcebus murinus lemur primate. Sci Rep 2012, 2:910.
13. Chandra S., Gallardo G., Fernandez-Chacon R., Schluter O.M., Sudhof T.C. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 2005, 123:383-396.
14. Chaudhuri K.R., Odin P. The challenge of non-motor symptoms in Parkinson's disease. Prog Brain Res 2010, 184:325-341.
15. Chaudhuri K.R., Odin P., Antonini A., Martinez-Martin P. Parkinson's disease: the non-motor issues. Parkinsonism Relat Disord 2011, 17:717-723.
16. Chu Y., Kordower J.H. Age-associated increases of alpha-synuclein in monkeys and humans are associated with nigrostriatal dopamine depletion: is this the target for Parkinson's disease?. Neurobiol Dis 2007, 25:134-149.
17. Chu Y., Kordower J.H. The prion hypothesis of Parkinson's disease. Curr Neurol Neurosci Rep 2015, 15:28.
18. Conway K.A., Lee S.J., Rochet J.C., Ding T.T., Williamson R.E., Lansbury P.T. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA 2000, 97:571-576.
19. Cooper O., Astradsson A., Hallett P., Robertson H., Mendez I., Isacson O. Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients. J Neurol 2009, 256(Suppl. 3):310-316.
20. Dauer W., Przedborski S. Parkinson's disease: mechanisms and models. Neuron 2003, 39:889-909.
21. Davis G.C., Williams A.C., Markey S.P., Ebert M.H., Caine E.D., Reichert C.M., et al. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1979, 1:249-254.
22. de Lau L.M., Breteler M.M. Epidemiology of Parkinson's disease. Lancet Neurol 2006, 5:525-535.
23. Decressac M., Mattsson B., Bjorklund A. Comparison of the behavioural and histological characteristics of the 6-OHDA and alpha-synuclein rat models of Parkinson's disease. Exp Neurol 2012, 235:306-315.
24. Ebrahimi-Fakhari D., Cantuti-Castelvetri I., Fan Z., Rockenstein E., Masliah E., Hyman B.T., et al. Distinct roles in vivo for the ubiquitin-proteasome system and the autophagy-lysosomal pathway in the degradation of alpha-synuclein. J Neurosci 2011, 31:14508-14520.
25. Emborg M.E. Nonhuman primate models of Parkinson's disease. ILAR J 2007, 48:339-355.
26. Emborg M.E., Kordower J.H. Aging in nonhuman primates. Interdisciplinary topics in gerontology 2002, 102-117. Karger, Basel/New York. J.M. Erwin, P.R. Hof (Eds.).
27. Emborg M.E., Ma S.Y., Mufson E.J., Levey A.I., Taylor M.D., Brown W.D., et al. Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. J Comp Neurol 1998, 401:253-265.
28. Eslamboli A., Georgievska B., Ridley R.M., Baker H.F., Muzyczka N., Burger C., et al. Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson's disease. J Neurosci 2005, 25:769-777.
29. Eslamboli A., Romero-Ramos M., Burger C., Bjorklund T., Muzyczka N., Mandel R.J., et al. Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain. Brain 2007, 130:799-815.
30. Fornai F., Schluter O.M., Lenzi P., Gesi M., Ruffoli R., Ferrucci M., et al. Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci USA 2005, 102:3413-3418.
31. Forno L.S., Langston J.W., DeLanney L.E., Irwin I., Ricaurte G.A. Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 1986, 20:449-455.
32. Fox S.H., Brotchie J.M. The MPTP-lesioned non-human primate models of Parkinson's disease. Past, present, and future. Prog Brain Res 2010, 184:133-157.
33. Fujiwara H., Hasegawa M., Dohmae N., Kawashima A., Masliah E., Goldberg M.S., et al. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 2002, 4:160-164.
34. Giasson B.I., Uryu K., Trojanowski J.Q., Lee V.M. Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 1999, 274:7619-7622.
35. Goldberg A.L. Protein degradation and protection against misfolded or damaged proteins. Nature 2003, 426:895-899.
36. Hallett P.J., Cooper O., Sadi D., Robertson H., Mendez I., Isacson O. Long-term health of dopaminergic neuron transplants in Parkinson's disease patients. Cell Rep 2014, 7:1755-1761.
37. Halliday G., Herrero M.T., Murphy K., McCann H., Ros-Bernal F., Barcia C., et al. No Lewy pathology in monkeys with over 10 years of severe MPTP Parkinsonism. Mov Disord 2009, 24:1519-1523.
38. Hamilton B.A. alpha-Synuclein A53T substitution associated with Parkinson disease also marks the divergence of Old World and New World primates. Genomics 2004, 83:739-742.
39. Hilker R., Brotchie J.M., Chapman J. Pros and cons of a prion-like pathogenesis in Parkinson's disease. BMC Neurol 2011, 11:74.
40. Irwin D.J., Abrams J.Y., Schonberger L.B., Leschek E.W., Mills J.L., Lee V.M., et al. Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 2013, 70:462-468.
41. Joers V., Dilley K., Rahman S., Jones C., Shultz J., Simmons H., et al. Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates. PLOS ONE 2014, 9:e104850.
42. Joers V., Emborg M.E. Modeling and imaging cardiac sympathetic neurodegeneration in Parkinson's disease. Am J Nucl Med Mol Imaging 2014, 4:125-159.
43. Joers V., Seneczko K., Goecks N.C., Kamp T.J., Hacker T.A., Brunner K.G., et al. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys. PLoS ONE 2012, 7:e35371.
44. Joers V., Vermilyea S., Dilley K., Emborg M.E. Systemic administration of 6-OHDA to rhesus monkeys upregulates HLA-DR expression in brain microvasculature. J Inflamm Res 2014, 7:139-149.
45. Kalia L.V., Lang A.E. Parkinson's disease. Lancet 2015, [Epub ahead of print]. 10.1016/S0140-6736(14)61393-3.
46. Kasten M., Klein C. The many faces of alpha-synuclein mutations. Mov Disord 2013, 28:697-701.
47. Kimmelman J., London A.J., Ravina B., Ramsay T., Bernstein M., Fine A., et al. Launching invasive, first-in-human trials against Parkinson's disease: ethical considerations. Mov Disord 2009, 24:1893-1901.
48. Kirik D., Annett L.E., Burger C., Muzyczka N., Mandel R.J., Bjorklund A. Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson's disease. Proc Natl Acad Sci USA 2003, 100:2884-2889.
49. Kirik D., Rosenblad C., Burger C., Lundberg C., Johansen T.E., Muzyczka N., et al. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 2002, 22:2780-2791.
50. Klein A., Gidyk D.C., Shriner A.M., Colwell K.L., Tatton N.A., Tatton W.G., et al. Dose-dependent loss of motor function after unilateral medial forebrain bundle rotenone lesion in rats: a cautionary note. Behav Brain Res 2011, 222:33-42.
51. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 2007, 8:931-937.
52. Koprich J.B., Johnston T.H., Reyes M.G., Sun X., Brotchie J.M. Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease. Mol Neurodegener 2010, 5:43.
53. Kordower J.H., Chu Y., Hauser R.A., Freeman T.B., Olanow C.W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med 2008, 14:504-506.
54. Kordower J.H., Kanaan N.M., Chu Y., Suresh Babu R., Stansell J., Terpstra B.T., et al. Failure of proteasome inhibitor administration to provide a model of Parkinson's disease in rats and monkeys. Ann Neurol 2006, 60:264-268.
55. Kordower J.H., Chu Y., Muller S., Tavares A., Barret O., Alagille D., et al. Intrastriatal alpha synuclein preformed fibrils in macaque monkeys: neuronal transport, long-term imaging and neuropathologic changes. Soc Neurosci Abstr 2014, 409.07/I11.
56. Kowall N.W., Hantraye P., Brouillet E., Beal M.F., McKee A.C., Ferrante R.J. MPTP induces alpha-synuclein aggregation in the substantia nigra of baboons. Neuroreport 2000, 11:211-213.
57. Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., et al. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 1998, 18:106-108.
58. Langston J.W. The Parkinson's complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006, 59:591-596.
59. Langston J.W., Ballard P., Tetrud J.W., Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983, 219:979-980.
60. Langston J.W., Forno L.S., Tetrud J., Reeves A.G., Kaplan J.A., Karluk D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 1999, 46:598-605.
61. Larsen K., Hedegaard C., Bertelsen M.F., Bendixen C. Threonine 53 in alpha-synuclein is conserved in long-living non-primate animals. Biochem Biophys Res Commun 2009, 387:602-605.
62. Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., et al. The ubiquitin pathway in Parkinson's disease. Nature 1998, 395:451-452.
63. Lesage S., Anheim M., Letournel F., Bousset L., Honore A., Rozas N., et al. G51D alpha-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol 2013, 4:459-471.
64. Li J.Y., Englund E., Holton J.L., Soulet D., Hagell P., Lees A.J., et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 2008, 14:501-503.
65. Li J.Y., Englund E., Widner H., Rehncrona S., Bjorklund A., Lindvall O., et al. Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson's disease. Mov Disord 2010, 25:1091-1096.
66. Lindgren H.S., Lelos M.J., Dunnett S.B. Do alpha-synuclein vector injections provide a better model of Parkinson's disease than the classic 6-hydroxydopamine model?. Exp Neurol 2012, 237:36-42.
67. London A.J., Kimmelman J., Emborg M.E. Research ethics. Beyond access vs. protection in trials of innovative therapies. Science 2010, 328:829-830.
68. Luk K.C., Kehm V., Carroll J., Zhang B., O'Brien P., Trojanowski J.Q., et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 2012, 338:949-953.
69. Luk K.C., Song C., O'Brien P., Stieber A., Branch J.R., Brunden K.R., et al. Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 2009, 106:20051-20056.
70. McCormack A.L., Mak S.K., Shenasa M., Langston W.J., Forno L.S., Di Monte D.A. Pathologic modifications of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated squirrel monkeys. J Neuropathol Exp Neurol 2008, 67:793-802.
71. McLean P.J., Kawamata H., Ribich S., Hyman B.T. Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson's disease-linked mutations. J Biol Chem 2000, 275:8812-8816.
72. McNaught K.S., Belizaire R., Isacson O., Jenner P., Olanow C.W. Altered proteasomal function in sporadic Parkinson's disease. Exp Neurol 2003, 179:38-46.
73. McNaught K.S., Perl D.P., Brownell A.L., Olanow C.W. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann Neurol 2004, 56:149-162.
74. Medina M., Avila J. The role of extracellular Tau in the spreading of neurofibrillary pathology. Front Cell Neurosci 2014, 8:113.
75. Mendez I., Vinuela A., Astradsson A., Mukhida K., Hallett P., Robertson H., et al. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med 2008, 14:507-509.
76. Mori F., Nishie M., Kakita A., Yoshimoto M., Takahashi H., Wakabayashi K. Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. J Neuropathol Exp Neurol 2006, 65:808-815.
77. Narhi L., Wood S.J., Steavenson S., Jiang Y., Wu G.M., Anafi D., et al. Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation. J Biol Chem 1999, 274:9843-9846.
78. Niu Y., Guo X., Chen Y., Wang C.E., Gao J., Yang W., et al. Early Parkinson's disease symptoms in alpha-synuclein transgenic monkeys. Hum Mol Genet 2015, 8:2308-2317.
79. Niu Y., Shen B., Cui Y., Chen Y., Wang J., Wang L., et al. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell 2014, 156:836-843.
80. Oueslati A., Fournier M., Lashuel H.A. Role of post-translational modifications in modulating the structure, function and toxicity of alpha-synuclein: implications for Parkinson's disease pathogenesis and therapies. Prog Brain Res 2010, 183:115-145.
81. Paleologou K.E., Oueslati A., Shakked G., Rospigliosi C.C., Kim H.Y., Lamberto G.R., et al. Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci 2010, 30:3184-3198.
82. Pan-Montojo F., Anichtchik O., Dening Y., Knels L., Pursche S., Jung R., et al. Progression of Parkinson's disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS ONE 2010, 5:e8762.
83. Pan-Montojo F., Schwarz M., Winkler C., Arnhold M., O'Sullivan G.A., Pal A., et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2012, 2:898.
84. Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997, 276:2045-2047.
85. Postuma R.B., Aarsland D., Barone P., Burn D.J., Hawkes C.H., Oertel W., et al. Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease. Mov Disord 2012, 27:617-626.
86. Priyadarshi A., Khuder S.A., Schaub E.A., Priyadarshi S.S. Environmental risk factors and Parkinson's disease: a metaanalysis. Environ Res 2001, 86:122-127.
87. Przedborski S., Vila M. MPTP: a review of its mechanisms of neurotoxicity. Clin Neurosci Res 2001, 1:407-418.
88. Purisai M.G., McCormack A.L., Langston W.J., Johnston L.C., Di Monte D.A. Alpha-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates. Neurobiol Dis 2005, 20:898-906.
89. Puschmann A. Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. Parkinsonism Relat Disord 2013, 19:407-415.
90. Rathke-Hartlieb S., Kahle P.J., Neumann M., Ozmen L., Haid S., Okochi M., et al. Sensitivity to MPTP is not increased in Parkinson's disease-associated mutant alpha-synuclein transgenic mice. J Neurochem 2001, 77:1181-1184.
91. Recasens A., Dehay B., Bové J., Carballo-Carbajal I., Dovero S., Pérez-Villalba A., et al. Lewy body extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 2014, 75(3):351-362.
92. Ridley R.M., Baker H.F., Windle C.P., Cummings R.M. Very long term studies of the seeding of beta-amyloidosis in primates. J Neural Transm 2006, 113:1243-1251.
93. Rott R., Szargel R., Haskin J., Bandopadhyay R., Lees A.J., Shani V., et al. alpha-Synuclein fate is determined by USP9X-regulated monoubiquitination. Proc Natl Acad Sci USA 2011, 108:18666-18671.
94. Schluter O.M., Fornai F., Alessandri M.G., Takamori S., Geppert M., Jahn R., et al. Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice. Neuroscience 2003, 118:985-1002.
95. Seidel K., Mahlke J., Siswanto S., Kruger R., Heinsen H., Auburger G., et al. The brainstem pathologies of Parkinson's disease and dementia with Lewy bodies. Brain Pathol 2015, 2:121-135.
96. Senoh S.W.B. Non-enzymatic conversions of dopamine to norepinephrine and trihydroxyphenethylamines. J Am Chem Soc 1959, 81:6222-6231.
97. Shannon K.M., Keshavarzian A., Dodiya H.B., Jakate S., Kordower J.H. Is alpha-synuclein in the colon a biomarker for premotor Parkinson's disease? Evidence from 3 cases. Mov Disord 2012, 27:716-719.
98. Sherer T.B., Kim J.H., Betarbet R., Greenamyre J.T. Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol 2003, 179:9-16.
99. Shimura H., Schlossmacher M.G., Hattori N., Frosch M.P., Trockenbacher A., Schneider R., et al. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science 2001, 293:263-269.
100. Singleton A.B., Farrer M., Johnson J., Singleton A., Hague S., Kachergus J., et al. alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003, 302:841.
101. Smith W.W., Margolis R.L., Li X., Troncoso J.C., Lee M.K., Dawson V.L., et al. Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells. J Neurosci 2005, 25:5544-5552.
102. Spillantini M.G., Crowther R.A., Jakes R., Hasegawa M., Goedert M. alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci USA 1998, 95:6469-6473.
103. Spillantini M.G., Schmidt M.L., Lee V.M., Trojanowski J.Q., Jakes R., Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997, 388:839-840.
104. Stefanis L., Larsen K.E., Rideout H.J., Sulzer D., Greene L.A. Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J Neurosci 2001, 21:9549-9560.
105. Stocchi F., Olanow C.W. Obstacles to the development of a neuroprotective therapy for Parkinson's disease. Mov Disord 2013, 28:3-7.
106. Tran L., Greenwood-Van Meerveld B. In a non-human primate model, aging disrupts the neural control of intestinal smooth muscle contractility in a region-specific manner. Neurogastroenterol Motil 2014, 26:410-418.
107. Ueda K., Fukushima H., Masliah E., Xia Y., Iwai A., Yoshimoto M., et al. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci USA 1993, 90:11282-11286.
108. Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 1968, 5:107-110.
109. Vila M., Vukosavic S., Jackson-Lewis V., Neystat M., Jakowec M., Przedborski S. Alpha-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP. J Neurochem 2000, 74:721-729.
110. Volpicelli-Daley L.A., Luk K.C., Patel T.P., Tanik S.A., Riddle D.M., Stieber A., et al. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011, 72:57-71.
111. Wakabayashi K., Tanji K., Mori F., Takahashi H. The Lewy body in Parkinson's disease: molecules implicated in the formation and degradation of alpha-synuclein aggregates. Neuropathology 2007, 27:494-506.
112. Watkin E.E., Arbez N., Waldron-Roby E., O'Meally R., Ratovitski T., Cole R.N., et al. Phosphorylation of mutant huntingtin at serine 116 modulates neuronal toxicity. PLOS ONE 2014, 9:e88284.
113. Waxman E.A., Giasson B.I. Characterization of kinases involved in the phosphorylation of aggregated alpha-synuclein. J Neurosci Res 2011, 89:231-247.
114. Winslow A.R., Chen C.W., Corrochano S., Acevedo-Arozena A., Gordon D.E., Peden A.A., et al. alpha-Synuclein impairs macroautophagy: implications for Parkinson's disease. J Cell Biol 2010, 190:1023-1037.
115. Xilouri M., Brekk O.R., Landeck N., Pitychoutis P.M., Papasilekas T., Papadopoulou-Daifoti Z., et al. Boosting chaperone-mediated autophagy in vivo mitigates alpha-synuclein-induced neurodegeneration. Brain 2013, 136:2130-2146.
116. Yang W., Wang G., Wang C.E., Guo X., Yin P., Gao J., et al. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain. J Neurosci 2015, 35:8345-8358.
117. Yu W.H., Matsuoka Y., Sziraki I., Hashim A., Lafrancois J., Sershen H., et al. Increased dopaminergic neuron sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in transgenic mice expressing mutant A53T alpha-synuclein. Neurochem Res 2008, 33:902-911.
118. Zarranz J.J., Alegre J., Gomez-Esteban J.C., Lezcano E., Ros R., Ampuero I., et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 2004, 55:164-173.