Gene-environment interactions: Key to unraveling the mystery of Parkinson's disease

Progress in Neurobiology

Volumn 94, Issue 1, 2011, Pages 1-19

  Gao, Hui Ming ^a   Hong, Jau Shyong ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

Animal models; Crosstalk among PD associated genetic pathways; Disease progression; Environmental cause of PD; Gene environment interactions; Genetics of PD; Microglia; Neurodegeneration; Neurodegenerative disorders; Neuroinflammation; Parkinson's disease

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; ALPHA SYNUCLEIN; DJ 1 PROTEIN; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; LEUCINE RICH REPEAT KINASE 2; LIPOPOLYSACCHARIDE; METHAMPHETAMINE; NEUROTOXIN; PARAQUAT; PARKIN; PESTICIDE; ROTENONE;

ARTICLE; DISEASE COURSE; DISEASE SURVEILLANCE; DNA POLYMORPHISM; ENCEPHALITIS; GENE IDENTIFICATION; GENE INACTIVATION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC ASSOCIATION; GENETIC ENGINEERING; GENOTYPE ENVIRONMENT INTERACTION; GLIA CELL; HUMAN; MOLECULAR INTERACTION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; PROTEIN AGGREGATION; TRAUMATIC BRAIN INJURY;

EID: 79953839752     PISSN: 03010082     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pneurobio.2011.03.005     Document Type: Review

References (316)

1. Abeliovich A., Schmitz Y., Farinas I., Choi-Lundberg D., Ho W.H., Castillo P.E., Shinsky N., Verdugo J.M., Armanini M., Ryan A., Hynes M., Phillips H., Sulzer D., Rosenthal A. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 2000, 25:239-252.
2. Ahn T.B., Kim S.Y., Kim J.Y., Park S.S., Lee D.S., Min H.J., Kim Y.K., Kim S.E., Kim J.M., Kim H.J., Cho J., Jeon B.S. alpha-Synuclein gene duplication is present in sporadic Parkinson disease. Neurology 2008, 70:43-49.
3. Alam M., Schmidt W.J. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behav. Brain Res. 2002, 136:317-324.
4. Andres-Mateos E., Perier C., Zhang L., Blanchard-Fillion B., Greco T.M., Thomas B., Ko H.S., Sasaki M., Ischiropoulos H., Przedborski S., Dawson T.M., Dawson V.L. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:14807-14812.
5. Andres-Mateos E., Mejias R., Sasaki M., Li X., Lin B.M., Biskup S., Zhang L., Banerjee R., Thomas B., Yang L., Liu G., Beal M.F., Huso D.L., Dawson T.M., Dawson V.L. Unexpected lack of hypersensitivity in LRRK2 knock-out mice to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). J. Neurosci. 2009, 29:15846-15850.
6. Ascherio A., Chen H., Weisskopf M.G., O'Reilly E., McCullough M.L., Calle E.E., Schwarzschild M.A., Thun M.J. Pesticide exposure and risk for Parkinson's disease. Ann. Neurol. 2006, 60:197-203.
7. Beilina A., Van Der Brug M., Ahmad R., Kesavapany S., Miller D.W., Petsko G.A., Cookson M.R. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:5703-5708.
8. Benamer H.T., de Silva R. LRRK2 G2019S in the North African population: a review. Eur. Neurol. 2010, 63:321-325.
9. Berger A.K., Cortese G.P., Amodeo K.D., Weihofen A., Letai A., LaVoie M.J. Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release. Hum. Mol. Genet. 2009, 18:4317-4328.
10. 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.
11. Betarbet R., Canet-Aviles R.M., Sherer T.B., Mastroberardino P.G., McLendon C., Kim J.H., Lund S., Na H.M., Taylor G., Bence N.F., Kopito R., Seo B.B., Yagi T., Yagi A., Klinefelter G., Cookson M.R., Greenamyre J.T. Intersecting pathways to neurodegeneration in Parkinson's disease: effects of the pesticide rotenone on DJ-1, alpha-synuclein, and the ubiquitin-proteasome system. Neurobiol. Dis. 2006, 22:404-420.
12. Bhatt M.H., Elias M.A., Mankodi A.K. Acute and reversible parkinsonism due to organophosphate pesticide intoxication: five cases. Neurology 1999, 52:1467-1471.
13. Boger H.A., Granholm A.C., McGinty J.F., Middaugh L.D. A dual-hit animal model for age-related parkinsonism. Prog. Neurobiol. 2010, 90:217-229.
14. Bonifati V. Genetics of parkinsonism. Parkinsonism Relat. Disord. 2007, 13(Suppl. 3):S233-241.
15. Bonifati V., Rizzu P., van Baren M.J., Schaap O., Breedveld G.J., Krieger E., Dekker M.C., Squitieri F., Ibanez P., Joosse M., van Dongen J.W., Vanacore N., van Swieten J.C., Brice A., Meco G., van Duijn C.M., Oostra B.A., Heutink P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 2003, 299:256-259.
16. Bonneh-Barkay D., Reaney S.H., Langston W.J., Di Monte D.A. Redox cycling of the herbicide paraquat in microglial cultures. Brain Res. Mol. Brain Res. 2005, 134:52-56.
17. Brooks A.I., Chadwick C.A., Gelbard H.A., Cory-Slechta D.A., Federoff H.J. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res. 1999, 823:1-10.
18. Brown T.P., Rumsby P.C., Capleton A.C., Rushton L., Levy L.S. Pesticides and Parkinson's disease-is there a link?. Environ. Health Perspect. 2006, 114:156-164.
19. Bruggemann N., Mitterer M., Lanthaler A.J., Djarmati A., Hagenah J., Wiegers K., Winkler S., Pawlack H., Lohnau T., Pramstaller P.P., Klein C., Lohmann K. Frequency of heterozygous Parkin mutations in healthy subjects: need for careful prospective follow-up examination of mutation carriers. Parkinsonism Relat. Disord. 2009, 15:425-429.
20. Burre J., Sharma M., Tsetsenis T., Buchman V., Etherton M.R., Sudhof T.C. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 2010, 329:1663-1667.
21. Cabin D.E., Gispert-Sanchez S., Murphy D., Auburger G., Myers R.R., Nussbaum R.L. Exacerbated synucleinopathy in mice expressing A53T SNCA on a Snca null background. Neurobiol. Aging 2005, 26:25-35.
22. Carmine Belin A., Westerlund M., Sydow O., Lundstromer K., Hakansson A., Nissbrandt H., Olson L., Galter D. Leucine-rich repeat kinase 2 (LRRK2) mutations in a Swedish Parkinson cohort and a healthy nonagenarian. Mov. Disord. 2006, 21:1731-1734.
23. Castano A., Herrera A.J., Cano J., Machado A. Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J. Neurochem. 1998, 70:1584-1592.
24. Chandra S., Fornai F., Kwon H.B., Yazdani U., Atasoy D., Liu X., Hammer R.E., Battaglia G., German D.C., Castillo P.E., Sudhof T.C. Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:14966-14971.
25. 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.
26. Chartier-Harlin M.C., 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. Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 2004, 364:1167-1169.
27. Checkoway H., Powers K., Smith-Weller T., Franklin G.M., Longstreth W.T., Swanson P.D. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am. J. Epidemiol. 2002, 155:732-738.
28. Chen H., Zhang S.M., Hernan M.A., Schwarzschild M.A., Willett W.C., Colditz G.A., Speizer F.E., Ascherio A. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch. Neurol. 2003, 60:1059-1064.
29. Chen H., Jacobs E., Schwarzschild M.A., McCullough M.L., Calle E.E., Thun M.J., Ascherio A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann. Neurol. 2005, 58:963-967.
30. Chen L., Cagniard B., Mathews T., Jones S., Koh H.C., Ding Y., Carvey P.M., Ling Z., Kang U.J., Zhuang X. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem. 2005, 280:21418-21426.
31. Chen H., O'Reilly E.J., Schwarzschild M.A., Ascherio A. Peripheral inflammatory biomarkers and risk of Parkinson's disease. Am. J. Epidemiol. 2008, 167:90-95.
32. Chen H., Huang X., Guo X., Mailman R.B., Park Y., Kamel F., Umbach D.M., Xu Q., Hollenbeck A., Schatzkin A., Blair A. Smoking duration, intensity, and risk of Parkinson disease. Neurology 2010, 74:878-884.
33. Chesselet M.F. In vivo alpha-synuclein overexpression in rodents: a useful model of Parkinson's disease?. Exp. Neurol. 2008, 209:22-27.
34. Chesselet M.F., Fleming S., Mortazavi F., Meurers B. Strengths and limitations of genetic mouse models of Parkinson's disease. Parkinsonism Relat. Disord. 2008, 14(Suppl. 2):S84-S87.
35. 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.
36. Chun H.S., Gibson G.E., DeGiorgio L.A., Zhang H., Kidd V.J., Son J.H. Dopaminergic cell death induced by MPP(+), oxidant and specific neurotoxicants shares the common molecular mechanism. J. Neurochem. 2001, 76:1010-1021.
37. Chung K.K., Thomas B., Li X., Pletnikova O., Troncoso J.C., Marsh L., Dawson V.L., Dawson T.M. S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function. Science 2004, 304:1328-1331.
38. Clark L.N., Afridi S., Mejia-Santana H., Harris J., Louis E.D., Cote L.J., Andrews H., Singleton A., Wavrant De-Vrieze F., Hardy J., Mayeux R., Fahn S., Waters C., Ford B., Frucht S., Ottman R., Marder K. Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations. Mov. Disord. 2004, 19:796-800.
39. Clark I.E., Dodson M.W., Jiang C., Cao J.H., Huh J.R., Seol J.H., Yoo S.J., Hay B.A., Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 2006, 441:1162-1166.
40. 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. U.S.A. 2000, 97:571-576.
41. Conway K.A., Rochet J.C., Bieganski R.M., Lansbury P.T. Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 2001, 294:1346-1349.
42. Cookson M.R. DJ-1, PINK1, and their effects on mitochondrial pathways. Mov. Disord. 2010, 25(Suppl. 1):S44-S48.
43. Cooper A.A., Gitler A.D., Cashikar A., Haynes C.M., Hill K.J., Bhullar B., Liu K., Xu K., Strathearn K.E., Liu F., Cao S., Caldwell K.A., Caldwell G.A., Marsischky G., Kolodner R.D., Labaer J., Rochet J.C., Bonini N.M., Lindquist S. Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 2006, 313:324-328.
44. Correia Guedes L., Ferreira J.J., Rosa M.M., Coelho M., Bonifati V., Sampaio C. Worldwide frequency of G2019S LRRK2 mutation in Parkinson's disease: a systematic review. Parkinsonism Relat. Disord. 2010, 16:237-242.
45. Corrigan F.M., Murray L., Wyatt C.L., Shore R.F. Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's disease. Exp. Neurol. 1998, 150:339-342.
46. Corrigan F.M., Wienburg C.L., Shore R.F., Daniel S.E., Mann D. Organochlorine insecticides in substantia nigra in Parkinson's disease. J. Toxicol. Environ. Health A 2000, 59:229-234.
47. Dauer W., Kholodilov N., Vila M., Trillat A.C., Goodchild R., Larsen K.E., Staal R., Tieu K., Schmitz Y., Yuan C.A., Rocha M., Jackson-Lewis V., Hersch S., Sulzer D., Przedborski S., Burke R., Hen R. Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:14524-14529.
48. Davidson W.S., Jonas A., Clayton D.F., George J.M. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 1998, 273:9443-9449.
49. Dawson T.M., Dawson V.L. The role of parkin in familial and sporadic Parkinson's disease. Mov. Disord. 2010, 25(Suppl. 1):S32-S39.
50. Dawson T.M., Ko H.S., Dawson V.L. Genetic animal models of Parkinson's disease. Neuron 2010, 66:646-661.
51. de Jong M.D., Bach V.C., Phan T.Q., Vo M.H., Tran T.T., Nguyen B.H., Beld M., Le T.P., Truong H.K., Nguyen V.V., Tran T.H., Do Q.H., Farrar J. Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma. N. Engl. J. Med. 2005, 352:686-691.
52. Dekker M.C., Eshuis S.A., Maguire R.P., Veenma-van der Duijn L., Pruim J., Snijders P.J., Oostra B.A., van Duijn C.M., Leenders K.L. PET neuroimaging and mutations in the DJ-1 gene. J. Neural Transm. 2004, 111:1575-1581.
53. Deng H., Dodson M.W., Huang H., Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:14503-14508.
54. Deng J., Lewis P.A., Greggio E., Sluch E., Beilina A., Cookson M.R. Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:1499-1504.
55. De Palma G., Mozzoni P., Mutti A., Calzetti S., Negrotti A. Case-control study of interactions between genetic and environmental factors in Parkinson's disease. Lancet 1998, 352:1986-1987.
56. Dhillon A.S., Tarbutton G.L., Levin J.L., Plotkin G.M., Lowry L.K., Nalbone J.T., Shepherd S. Pesticide/environmental exposures and Parkinson's disease in East Texas. J. Agromed. 2008, 13:37-48.
57. Di Fonzo A., Rohe C.F., Ferreira J., Chien H.F., Vacca L., Stocchi F., Guedes L., Fabrizio E., Manfredi M., Vanacore N., Goldwurm S., Breedveld G., Sampaio C., Meco G., Barbosa E., Oostra B.A., Bonifati V. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 2005, 365:412-415.
58. Dibble L.E., Addison O., Papa E. The effects of exercise on balance in persons with Parkinson's disease: a systematic review across the disability spectrum. J. Neurol. Phys. Ther. 2009, 33:14-26.
59. Dick F.D., De Palma G., Ahmadi A., Osborne A., Scott N.W., Prescott G.J., Bennett J., Semple S., Dick S., Mozzoni P., Haites N., Wettinger S.B., Mutti A., Otelea M., Seaton A., Soderkvist P., Felice A. Gene-environment interactions in parkinsonism and Parkinson's disease: the Geoparkinson study. Occup. Environ. Med. 2007, 64:673-680.
60. Djarmati A., Hedrich K., Svetel M., Lohnau T., Schwinger E., Romac S., Pramstaller P.P., Kostic V., Klein C. Heterozygous PINK1 mutations: a susceptibility factor for Parkinson disease?. Mov. Disord. 2006, 21:1526-1530.
61. Doder M., Jahanshahi M., Turjanski N., Moseley I.F., Lees A.J. Parkinson's syndrome after closed head injury: a single case report. J. Neurol. Neurosurg. Psychiatry 1999, 66:380-385.
62. Duvoisin R.C., Lobo-Antunes J., Yahr M.D. Response of patients with postencephalitic Parkinsonism to levodopa. J. Neurol. Neurosurg. Psychiatry 1972, 35:487-495.
63. Duvoisin R.C., Eldridge R., Williams A., Nutt J., Calne D. Twin study of Parkinson disease. Neurology 1981, 31:77-80.
64. Earley F.G., Ragan C.I. Photoaffinity labelling of mitochondrial NADH dehydrogenase with arylazidoamorphigenin, an analogue of rotenone. Biochem. J. 1984, 224:525-534.
65. Edwards T.L., Scott W.K., Almonte C., Burt A., Powell E.H., Beecham G.W., Wang L., Zuchner S., Konidari I., Wang G., Singer C., Nahab F., Scott B., Stajich J.M., Pericak-Vance M., Haines J., Vance J.M., Martin E.R. Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann. Hum. Genet. 2010, 74:97-109.
66. Elbaz A., Clavel J., Rathouz P.J., Moisan F., Galanaud J.P., Delemotte B., Alperovitch A., Tzourio C. Professional exposure to pesticides and Parkinson disease. Ann. Neurol. 2009, 66:494-504.
67. Elizan T.S., Casals J. Astrogliosis in von Economo's and postencephalitic Parkinson's diseases supports probable viral etiology. J. Neurol. Sci. 1991, 105:131-134.
68. Engel L.S., Checkoway H., Keifer M.C., Seixas N.S., Longstreth W.T., Scott K.C., Hudnell K., Anger W.K., Camicioli R. Parkinsonism and occupational exposure to pesticides. Occup. Environ. Med. 2001, 58:582-589.
69. Exner N., Treske B., Paquet D., Holmstrom K., Schiesling C., Gispert S., Carballo-Carbajal I., Berg D., Hoepken H.H., Gasser T., Kruger R., Winklhofer K.F., Vogel F., Reichert A.S., Auburger G., Kahle P.J., Schmid B., Haass C. Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin. J. Neurosci. 2007, 27:12413-12418.
70. Farrer M.J. Genetics of Parkinson disease: paradigm shifts and future prospects. Nat. Rev. Genet. 2006, 7:306-318.
71. Farrer M., Kachergus J., Forno L., Lincoln S., Wang D.S., Hulihan M., Maraganore D., Gwinn-Hardy K., Wszolek Z., Dickson D., Langston J.W. Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann. Neurol. 2004, 55:174-179.
72. Feany M.B., Bender W.W. A Drosophila model of Parkinson's disease. Nature 2000, 404:394-398.
73. Ferrante R.J., Schulz J.B., Kowall N.W., Beal M.F. Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra. Brain Res. 1997, 753:157-162.
74. Fleming L., Mann J.B., Bean J., Briggle T., Sanchez-Ramos J.R. Parkinson's disease and brain levels of organochlorine pesticides. Ann. Neurol. 1994, 36:100-103.
75. Forman M.S., Lee V.M., Trojanowski J.Q. Nosology of Parkinson's disease: looking for the way out of a quagmire. Neuron 2005, 47:479-482.
76. Fornai F., Schluter O.M., Lenzi P., Gesi M., Ruffoli R., Ferrucci M., Lazzeri G., Busceti C.L., Pontarelli F., Battaglia G., Pellegrini A., Nicoletti F., Ruggieri S., Paparelli A., Sudhof T.C. Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:3413-3418.
77. 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.
78. Frank-Cannon T.C., Tran T., Ruhn K.A., Martinez T.N., Hong J., Marvin M., Hartley M., Trevino I., O'Brien D.E., Casey B., Goldberg M.S., Tansey M.G. Parkin deficiency increases vulnerability to inflammation-related nigral degeneration. J. Neurosci. 2008, 28:10825-10834.
79. Friedman J.H. Progressive parkinsonism in boxers. South Med. J. 1989, 82:543-546.
80. Fukushima T., Tawara T., Isobe A., Hojo N., Shiwaku K., Yamane Y. Radical formation site of cerebral complex I and Parkinson's disease. J. Neurosci. Res. 1995, 42:385-390.
81. Gambotto A., Barratt-Boyes S.M., de Jong M.D., Neumann G., Kawaoka Y. Human infection with highly pathogenic H5N1 influenza virus. Lancet 2008, 371:1464-1475.
82. Gandhi S., Wood-Kaczmar A., Yao Z., Plun-Favreau H., Deas E., Klupsch K., Downward J., Latchman D.S., Tabrizi S.J., Wood N.W., Duchen M.R., Abramov A.Y. PINK1-associated Parkinson's disease is caused by neuronal vulnerability to calcium-induced cell death. Mol. Cell 2009, 33:627-638.
83. Gao H.M., Hong J.S., Zhang W., Liu B. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J. Neurosci. 2002, 22:782-790.
84. Gao H.M., Jiang J., Wilson B., Zhang W., Hong J.S., Liu B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J. Neurochem. 2002, 81:1285-1297.
85. Gao H.M., Kotzbauer P.T., Uryu K., Leight S., Trojanowski J.Q., Lee V.M. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J. Neurosci. 2008, 28:7687-7698.
86. Gao H.M., Zhang F., Zhou H., Kam W., Wilson B., Hong J.S. Neuroinflammation and alpha-synuclein dysfunction potentiate each other driving chronic progression of neurodegeneration in a mouse model of Parkinson's disease. Environ. Health Perspect., in press 2011.
87. Gautier C.A., Kitada T., Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:11364-11369.
88. Gehrke S., Imai Y., Sokol N., Lu B. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 2010, 466:637-641.
89. Gelmetti V., Ferraris A., Brusa L., Romano F., Lombardi F., Barzaghi C., Stanzione P., Garavaglia B., Dallapiccola B., Valente E.M. Late onset sporadic Parkinson's disease caused by PINK1 mutations: clinical and functional study. Mov. Disord. 2008, 23:881-885.
90. Gerecke K.M., Jiao Y., Pani A., Pagala V., Smeyne R.J. Exercise protects against MPTP-induced neurotoxicity in mice. Brain Res. 2010, 1341:72-83.
91. Ghaemi M., Rudolf J., Schmulling S., Bamborschke S., Heiss W.D. FDG- and Dopa-PET in postencephalitic parkinsonism. J. Neural Transm. 2000, 107:1289-1295.
92. Gilks W.P., Abou-Sleiman P.M., Gandhi S., Jain S., Singleton A., Lees A.J., Shaw K., Bhatia K.P., Bonifati V., Quinn N.P., Lynch J., Healy D.G., Holton J.L., Revesz T., Wood N.W. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 2005, 365:415-416.
93. Gispert S., Ricciardi F., Kurz A., Azizov M., Hoepken H.H., Becker D., Voos W., Leuner K., Muller W.E., Kudin A.P., Kunz W.S., Zimmermann A., Roeper J., Wenzel D., Jendrach M., Garcia-Arencibia M., Fernandez-Ruiz J., Huber L., Rohrer H., Barrera M., Reichert A.S., Rub U., Chen A., Nussbaum R.L., Auburger G. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One 2009, 4:e5777.
94. Gitler A.D., Bevis B.J., Shorter J., Strathearn K.E., Hamamichi S., Su L.J., Caldwell K.A., Caldwell G.A., Rochet J.C., McCaffery J.M., Barlowe C., Lindquist S. The Parkinson's disease protein alpha-synuclein disrupts cellular Rab homeostasis. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:145-150.
95. Gloeckner C.J., Kinkl N., Schumacher A., Braun R.J., O'Neill E., Meitinger T., Kolch W., Prokisch H., Ueffing M. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum. Mol. Genet. 2006, 15:223-232.
96. Gobbi L.T., Oliveira-Ferreira M.D., Caetano M.J., Lirani-Silva E., Barbieri F.A., Stella F., Gobbi S. Exercise programs improve mobility and balance in people with Parkinson's disease. Parkinsonism Relat. Disord. 2009, 15(Suppl. 3):S49-S52.
97. Goetz C.G., Pappert E.J. Trauma and movement disorders. Neurol. Clin. 1992, 10:907-919.
98. Goldberg M.S., Fleming S.M., Palacino J.J., Cepeda C., Lam H.A., Bhatnagar A., Meloni E.G., Wu N., Ackerson L.C., Klapstein G.J., Gajendiran M., Roth B.L., Chesselet M.F., Maidment N.T., Levine M.S., Shen J. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J. Biol. Chem. 2003, 278:43628-43635.
99. Goldberg M.S., Pisani A., Haburcak M., Vortherms T.A., Kitada T., Costa C., Tong Y., Martella G., Tscherter A., Martins A., Bernardi G., Roth B.L., Pothos E.N., Calabresi P., Shen J. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 2005, 45:489-496.
100. Goldman S.M., Tanner C.M., Oakes D., Bhudhikanok G.S., Gupta A., Langston J.W. Head injury and Parkinson's disease risk in twins. Ann. Neurol. 2006, 60:65-72.
101. Gorell J.M., Johnson C.C., Rybicki B.A., Peterson E.L., Richardson R.J. The risk of Parkinson's disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998, 50:1346-1350.
102. Greene J.C., Whitworth A.J., Kuo I., Andrews L.A., Feany M.B., Pallanck L.J. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl. Acad. Sci. U.S.A. 2003, 100:4078-4083.
103. Greggio E., Jain S., Kingsbury A., Bandopadhyay R., Lewis P., Kaganovich A., van der Brug M.P., Beilina A., Blackinton J., Thomas K.J., Ahmad R., Miller D.W., Kesavapany S., Singleton A., Lees A., Harvey R.J., Harvey K., Cookson M.R. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis. 2006, 23:329-341.
104. Greggio E., Zambrano I., Kaganovich A., Beilina A., Taymans J.M., Daniels V., Lewis P., Jain S., Ding J., Syed A., Thomas K.J., Baekelandt V., Cookson M.R. The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J. Biol. Chem. 2008, 283:16906-16914.
105. Guterman A., Smith R.W. Neurological sequelae of boxing. Sports Med. 1987, 4:194-210.
106. Hague S., Rogaeva E., Hernandez D., Gulick C., Singleton A., Hanson M., Johnson J., Weiser R., Gallardo M., Ravina B., Gwinn-Hardy K., Crawley A., St George-Hyslop P.H., Lang A.E., Heutink P., Bonifati V., Hardy J., Singleton A. Early-onset Parkinson's disease caused by a compound heterozygous DJ-1 mutation. Ann. Neurol. 2003, 54:271-274.
107. Hamza T.H., Zabetian C.P., Tenesa A., Laederach A., Montimurro J., Yearout D., Kay D.M., Doheny K.F., Paschall J., Pugh E., Kusel V.I., Collura R., Roberts J., Griffith A., Samii A., Scott W.K., Nutt J., Factor S.A., Payami H. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease. Nat. Genet. 2010, 42:781-785.
108. Hancock D.B., Martin E.R., Fujiwara K., Stacy M.A., Scott B.L., Stajich J.M., Jewett R., Li Y.J., Hauser M.A., Vance J.M., Scott W.K. NOS2A and the modulating effect of cigarette smoking in Parkinson's disease. Ann. Neurol. 2006, 60:366-373.
109. Hancock D.B., Martin E.R., Vance J.M., Scott W.K. Nitric oxide synthase genes and their interactions with environmental factors in Parkinson's disease. Neurogenetics 2008, 9:249-262.
110. Healy D.G., Abou-Sleiman P.M., Ahmadi K.R., Muqit M.M., Bhatia K.P., Quinn N.P., Lees A.J., Latchmann D.S., Goldstein D.B., Wood N.W. The gene responsible for PARK6 Parkinson's disease, PINK1, does not influence common forms of parkinsonism. Ann. Neurol. 2004, 56:329-335.
111. Healy D.G., Falchi M., O'Sullivan S.S., Bonifati V., Durr A., Bressman S., Brice A., Aasly J., Zabetian C.P., Goldwurm S., Ferreira J.J., Tolosa E., Kay D.M., Klein C., Williams D.R., Marras C., Lang A.E., Wszolek Z.K., Berciano J., Schapira A.H., Lynch T., Bhatia K.P., Gasser T., Lees A.J., Wood N.W. Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study. Lancet Neurol. 2008, 7:583-590.
112. Heikkila R.E., Nicklas W.J., Vyas I., Duvoisin R.C. Dopaminergic toxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats: implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Neurosci. Lett. 1985, 62:389-394.
113. Henry J., Smeyne R.J., Jang H., Miller B., Okun M.S. Parkinsonism and neurological manifestations of influenza throughout the 20th and 21st centuries. Parkinsonism Relat. Disord. 2010, 16:566-571.
114. Hernan M.A., Takkouche B., Caamano-Isorna F., Gestal-Otero J.J. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Ann. Neurol. 2002, 52:276-284.
115. Hoglinger G.U., Feger J., Prigent A., Michel P.P., Parain K., Champy P., Ruberg M., Oertel W.H., Hirsch E.C. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J. Neurochem. 2003, 84:491-502.
116. Horowitz M.P., Greenamyre J.T. Gene-environment interactions in Parkinson's disease: the importance of animal modeling. Clin. Pharmacol. Ther. 2010, 88:467-474.
117. Hu C.J., Sung S.M., Liu H.C., Lee C.C., Tsai C.H., Chang J.G. Polymorphisms of the parkin gene in sporadic Parkinson's disease among Chinese in Taiwan. Eur. Neurol. 2000, 44:90-93.
118. Hulihan M.M., Ishihara-Paul L., Kachergus J., Warren L., Amouri R., Elango R., Prinjha R.K., Upmanyu R., Kefi M., Zouari M., Sassi S.B., Yahmed S.B., El Euch-Fayeche G., Matthews P.M., Middleton L.T., Gibson R.A., Hentati F., Farrer M.J. LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study. Lancet Neurol. 2008, 7:591-594.
119. Iaccarino C., Crosio C., Vitale C., Sanna G., Carri M.T., Barone P. Apoptotic mechanisms in mutant LRRK2-mediated cell death. Hum. Mol. Genet. 2007, 16:1319-1326.
120. Ibanez P., Bonnet A.M., Debarges B., Lohmann E., Tison F., Pollak P., Agid Y., Durr A., Brice A. Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet 2004, 364:1169-1171.
121. Imai Y., Soda M., Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 2000, 275:35661-35664.
122. Itier J.M., Ibanez P., Mena M.A., Abbas N., Cohen-Salmon C., Bohme G.A., Laville M., Pratt J., Corti O., Pradier L., Ret G., Joubert C., Periquet M., Araujo F., Negroni J., Casarejos M.J., Canals S., Solano R., Serrano A., Gallego E., Sanchez M., Denefle P., Benavides J., Tremp G., Rooney T.A., Brice A., de Yebenes J.G. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum. Mol. Genet. 2003, 12:2277-2291.
123. Jackson-Lewis V., Przedborski S. Protocol for the MPTP mouse model of Parkinson's disease. Nat. Protoc. 2007, 2:141-151.
124. Jang H., Boltz D., Sturm-Ramirez K., Shepherd K.R., Jiao Y., Webster R., Smeyne R.J. Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:14063-14068.
125. Javoy F., Sotelo C., Herbet A., Agid Y. Specificity of dopaminergic neuronal degeneration induced by intracerebral injection of 6-hydroxydopamine in the nigrostriatal dopamine system. Brain Res. 1976, 102:201-215.
126. Jeon B.S., Jackson-Lewis V., Burke R.E. 6-Hydroxydopamine lesion of the rat substantia nigra: time course and morphology of cell death. Neurodegeneration 1995, 4:131-137.
127. Kahle P.J., Waak J., Gasser T. DJ-1 and prevention of oxidative stress in Parkinson's disease and other age-related disorders. Free Radic. Biol. Med. 2009, 47:1354-1361.
128. Kamel F., Tanner C., Umbach D., Hoppin J., Alavanja M., Blair A., Comyns K., Goldman S., Korell M., Langston J., Ross G., Sandler D. Pesticide exposure and self-reported Parkinson's disease in the agricultural health study. Am. J. Epidemiol. 2007, 165:364-374.
129. Kamp F., Exner N., Lutz A.K., Wender N., Hegermann J., Brunner B., Nuscher B., Bartels T., Giese A., Beyer K., Eimer S., Winklhofer K.F., Haass C. Inhibition of mitochondrial fusion by alpha-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J. 2010, 29:3571-3589.
130. Kay D.M., Zabetian C.P., Factor S.A., Nutt J.G., Samii A., Griffith A., Bird T.D., Kramer P., Higgins D.S., Payami H. Parkinson's disease and LRRK2: frequency of a common mutation in U.S. movement disorder clinics. Mov. Disord. 2006, 21:519-523.
131. Kay D.M., Moran D., Moses L., Poorkaj P., Zabetian C.P., Nutt J., Factor S.A., Yu C.E., Montimurro J.S., Keefe R.G., Schellenberg G.D., Payami H. Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients. Ann. Neurol. 2007, 61:47-54.
132. Kelada S.N., Checkoway H., Kardia S.L., Carlson C.S., Costa-Mallen P., Eaton D.L., Firestone J., Powers K.M., Swanson P.D., Franklin G.M., Longstreth W.T., Weller T.S., Afsharinejad Z., Costa L.G. 5′ and 3′ region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study. Hum. Mol. Genet. 2006, 15:3055-3062.
133. Khan N.L., Valente E.M., Bentivoglio A.R., Wood N.W., Albanese A., Brooks D.J., Piccini P. Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an 18F-DOPA PET study. Ann. Neurol.Ann. Neurol. 2002, 52:849-853.
134. Khan N.L., Horta W., Eunson L., Graham E., Johnson J.O., Chang S., Davis M., Singleton A., Wood N.W., Lees A.J. Parkin disease in a Brazilian kindred: manifesting heterozygotes and clinical follow-up over 10 years. Mov. Disord. 2005, 20:479-484.
135. Kim W.G., Mohney R.P., Wilson B., Jeohn G.H., Liu B., Hong J.S. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J. Neurosci. 2000, 20:6309-6316.
136. Kim R.H., Smith P.D., Aleyasin H., Hayley S., Mount M.P., Pownall S., Wakeham A., You-Ten A.J., Kalia S.K., Horne P., Westaway D., Lozano A.M., Anisman H., Park D.S., Mak T.W. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:5215-5220.
137. Kirik D., Rosenblad C., Burger C., Lundberg C., Johansen T.E., Muzyczka N., Mandel R.J., Bjorklund A. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J. Neurosci. 2002, 22:2780-2791.
138. Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998, 392:605-608.
139. Kitada T., Pisani A., Porter D.R., Yamaguchi H., Tscherter A., Martella G., Bonsi P., Zhang C., Pothos E.N., Shen J. Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:11441-11446.
140. Klein R.L., King M.A., Hamby M.E., Meyer E.M. Dopaminergic cell loss induced by human A30P alpha-synuclein gene transfer to the rat substantia nigra. Hum. Gene Ther. 2002, 13:605-612.
141. Klein C., Lohmann-Hedrich K., Rogaeva E., Schlossmacher M.G., Lang A.E. Deciphering the role of heterozygous mutations in genes associated with parkinsonism. Lancet Neurol. 2007, 6:652-662.
142. Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., Przuntek H., Epplen J.T., Schols L., Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat. Genet. 1998, 18:106-108.
143. 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.
144. LaVoie M.J., Ostaszewski B.L., Weihofen A., Schlossmacher M.G., Selkoe D.J. Dopamine covalently modifies and functionally inactivates parkin. Nat. Med. 2005, 11:1214-1221.
145. Lawson L.J., Perry V.H., Dri P., Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 1990, 39:151-170.
146. Lee V.M., Trojanowski J.Q. Mechanisms of Parkinson's disease linked to pathological alpha-synuclein: new targets for drug discovery. Neuron 2006, 52:33-38.
147. Lee S.B., Kim W., Lee S., Chung J. Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochem. Biophys. Res. Commun. 2007, 358:534-539.
148. Lesage S., Brice A. Parkinson's disease: from monogenic forms to genetic susceptibility factors. Hum. Mol. Genet. 2009, 18:R48-R59.
149. Lesage S., Ibanez P., Lohmann E., Pollak P., Tison F., Tazir M., Leutenegger A.L., Guimaraes J., Bonnet A.M., Agid Y., Durr A., Brice A. G2019S LRRK2 mutation in French and North African families with Parkinson's disease. Ann. Neurol. 2005, 58:784-787.
150. Lesage S., Durr A., Tazir M., Lohmann E., Leutenegger A.L., Janin S., Pollak P., Brice A. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N. Engl. J. Med. 2006, 354:422-423.
151. Lesage S., Belarbi S., Troiano A., Condroyer C., Hecham N., Pollak P., Lohman E., Benhassine T., Ysmail-Dahlouk F., Durr A., Tazir M., Brice A. Is the common LRRK2 G2019S mutation related to dyskinesias in North African Parkinson disease?. Neurology 2008, 71:1550-1552.
152. Lesage S., Lohmann E., Tison F., Durif F., Durr A., Brice A. Rare heterozygous parkin variants in French early-onset Parkinson disease patients and controls. J. Med. Genet. 2008, 45:43-46.
153. Levecque C., Elbaz A., Clavel J., Richard F., Vidal J.S., Amouyel P., Tzourio C., Alperovitch A., Chartier-Harlin M.C. Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study. Hum. Mol. Genet. 2003, 12:79-86.
154. Li J.Y., Englund E., Holton J.L., Soulet D., Hagell P., Lees A.J., Lashley T., Quinn N.P., Rehncrona S., Bjorklund A., Widner H., Revesz T., Lindvall O., Brundin P. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat. Med. 2008, 14:501-503.
155. Li Y., Liu W., Oo T.F., Wang L., Tang Y., Jackson-Lewis V., Zhou C., Geghman K., Bogdanov M., Przedborski S., Beal M.F., Burke R.E., Li C. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat. Neurosci. 2009, 12:826-828.
156. Li X., Patel J.C., Wang J., Avshalumov M.V., Nicholson C., Buxbaum J.D., Elder G.A., Rice M.E., Yue Z. Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson's disease mutation G2019S. J. Neurosci. 2010, 30:1788-1797.
157. Liberek K., Lewandowska A., Zietkiewicz S. Chaperones in control of protein disaggregation. EMBO J. 2008, 27:328-335.
158. Lim K.L., Ng C.H. Genetic models of Parkinson disease. Biochim. Biophys. Acta 2009, 1792:604-615.
159. Lin X., Parisiadou L., Gu X.L., Wang L., Shim H., Sun L., Xie C., Long C.X., Yang W.J., Ding J., Chen Z.Z., Gallant P.E., Tao-Cheng J.H., Rudow G., Troncoso J.C., Liu Z., Li Z., Cai H. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 2009, 64:807-827.
160. Ling Z., Gayle D.A., Ma S.Y., Lipton J.W., Tong C.W., Hong J.S., Carvey P.M. In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain. Mov. Disord. 2002, 17:116-124.
161. Ling Z., Zhu Y., Tong C., Snyder J.A., Lipton J.W., Carvey P.M. Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally. Exp. Neurol. 2006, 199:499-512.
162. Liou H.H., Chen R.C., Tsai Y.F., Chen W.P., Chang Y.C., Tsai M.C. Effects of paraquat on the substantia nigra of the wistar rats: neurochemical, histological, and behavioral studies. Toxicol. Appl. Pharmacol. 1996, 137:34-41.
163. Liou H.H., Tsai M.C., Chen C.J., Jeng J.S., Chang Y.C., Chen S.Y., Chen R.C. Environmental risk factors and Parkinson's disease: a case-control study in Taiwan. Neurology 1997, 48:1583-1588.
164. Liou A.K., Leak R.K., Li L., Zigmond M.J. Wild-type LRRK2 but not its mutant attenuates stress-induced cell death via ERK pathway. Neurobiol. Dis. 2008, 32:116-124.
165. Liu B., Du L., Hong J.S. Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J. Pharmacol. Exp. Ther. 2000, 293:607-617.
166. Liu B., Gao H.M., Hong J.S. Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environ. Health Perspect. 2003, 111:1065-1073.
167. Liu S., Ninan I., Antonova I., Battaglia F., Trinchese F., Narasanna A., Kolodilov N., Dauer W., Hawkins R.D., Arancio O. alpha-Synuclein produces a long-lasting increase in neurotransmitter release. EMBO J. 2004, 23:4506-4516.
168. Liu Z., Wang X., Yu Y., Li X., Wang T., Jiang H., Ren Q., Jiao Y., Sawa A., Moran T., Ross C.A., Montell C., Smith W.W. A Drosophila model for LRRK2-linked parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:2693-2698.
169. Liu W., Vives-Bauza C., Acin-Perez R., Yamamoto A., Tan Y., Li Y., Magrane J., Stavarache M.A., Shaffer S., Chang S., Kaplitt M.G., Huang X.Y., Beal M.F., Manfredi G., Li C. PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease. PLoS One 2009, 4:e4597.
170. Liu, M., Dobson, B., Glicksman, M.A., Yue, Z., Stein, R.L., 2010. Kinetic mechanistic studies of wild-type leucine-rich repeat kinase 2: characterization of the kinase and GTPase activities. Biochemistry 49, 2008-2017.
171. Lo Bianco C., Ridet J.L., Schneider B.L., Deglon N., Aebischer P. alpha-Synucleinopathy and selective dopaminergic neuron loss in a rat lentiviral-based model of Parkinson's disease. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:10813-10818.
172. Lockhart P.J., Lincoln S., Hulihan M., Kachergus J., Wilkes K., Bisceglio G., Mash D.C., Farrer M.J. DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J. Med. Genet. 2004, 41:e22.
173. Lu B., Vogel H. Drosophila models of neurodegenerative diseases. Annu. Rev. Pathol. 2009, 4:315-342.
174. Lu X.H., Fleming S.M., Meurers B., Ackerson L.C., Mortazavi F., Lo V., Hernandez D., Sulzer D., Jackson G.R., Maidment N.T., Chesselet M.F., Yang X.W. Bacterial artificial chromosome transgenic mice expressing a truncated mutant parkin exhibit age-dependent hypokinetic motor deficits, dopaminergic neuron degeneration, and accumulation of proteinase K-resistant alpha-synuclein. J. Neurosci. 2009, 29:1962-1976.
175. Lucking C.B., Durr A., Bonifati V., Vaughan J., De Michele G., Gasser T., Harhangi B.S., Meco G., Denefle P., Wood N.W., Agid Y., Brice A. Association between early-onset Parkinson's disease and mutations in the parkin gene. N. Engl. J. Med. 2000, 342:1560-1567.
176. Lucking C.B., Chesneau V., Lohmann E., Verpillat P., Dulac C., Bonnet A.M., Gasparini F., Agid Y., Durr A., Brice A. Coding polymorphisms in the parkin gene and susceptibility to Parkinson disease. Arch. Neurol. 2003, 60:1253-1256.
177. Macedo M.G., Anar B., Bronner I.F., Cannella M., Squitieri F., Bonifati V., Hoogeveen A., Heutink P., Rizzu P. The DJ-1L166P mutant protein associated with early onset Parkinson's disease is unstable and forms higher-order protein complexes. Hum. Mol. Genet. 2003, 12:2807-2816.
178. MacLeod D., Dowman J., Hammond R., Leete T., Inoue K., Abeliovich A. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 2006, 52:587-593.
179. Manning-Bog A.B., Langston J.W. Model fusion, the next phase in developing animal models for Parkinson's disease. Neurotox. Res. 2007, 11:219-240.
180. Manning-Bog A.B., McCormack A.L., Li J., Uversky V.N., Fink A.L., Di Monte D.A. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J. Biol. Chem. 2002, 277:1641-1644.
181. Manning-Bog A.B., McCormack A.L., Purisai M.G., Bolin L.M., Di Monte D.A. Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration. J. Neurosci. 2003, 23:3095-3099.
182. Maraganore D.M., de Andrade M., Lesnick T.G., Strain K.J., Farrer M.J., Rocca W.A., Pant P.V., Frazer K.A., Cox D.R., Ballinger D.G. High-resolution whole-genome association study of Parkinson disease. Am. J. Hum. Genet. 2005, 77:685-693.
183. Maries E., Dass B., Collier T.J., Kordower J.H., Steece-Collier K. The role of alpha-synuclein in Parkinson's disease: insights from animal models. Nat. Rev. Neurosci. 2003, 4:727-738.
184. Marongiu R., Ferraris A., Ialongo T., Michiorri S., Soleti F., Ferrari F., Elia A.E., Ghezzi D., Albanese A., Altavista M.C., Antonini A., Barone P., Brusa L., Cortelli P., Martinelli P., Pellecchia M.T., Pezzoli G., Scaglione C., Stanzione P., Tinazzi M., Zecchinelli A., Zeviani M., Cassetta E., Garavaglia B., Dallapiccola B., Bentivoglio A.R., Valente E.M. PINK1 heterozygous rare variants: prevalence, significance and phenotypic spectrum. Hum. Mutat. 2008, 29:565.
185. Martinez-Vicente M., Talloczy Z., Kaushik S., Massey A.C., Mazzulli J., Mosharov E.V., Hodara R., Fredenburg R., Wu D.C., Follenzi A., Dauer W., Przedborski S., Ischiropoulos H., Lansbury P.T., Sulzer D., Cuervo A.M. Dopamine-modified alpha-synuclein blocks chaperone-mediated autophagy. J. Clin. Invest. 2008, 118:777-788.
186. Marttila R.J., Kaprio J., Koskenvuo M., Rinne U.K. Parkinson's disease in a nationwide twin cohort. Neurology 1988, 38:1217-1219.
187. Masliah E., Rockenstein E., Veinbergs I., Mallory M., Hashimoto M., Takeda A., Sagara Y., Sisk A., Mucke L. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 2000, 287:1265-1269.
188. Mata I.F., Wedemeyer W.J., Farrer M.J., Taylor J.P., Gallo K.A. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci. 2006, 29:286-293.
189. 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.
190. McCulloch C.C., Kay D.M., Factor S.A., Samii A., Nutt J.G., Higgins D.S., Griffith A., Roberts J.W., Leis B.C., Montimurro J.S., Zabetian C.P., Payami H. Exploring gene-environment interactions in Parkinson's disease. Hum. Genet. 2008, 123:257-265.
191. Meco G., Bonifati V., Vanacore N., Fabrizio E. Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Scand. J. Work Environ. Health 1994, 20:301-305.
192. Mendez I., Vinuela A., Astradsson A., Mukhida K., Hallett P., Robertson H., Tierney T., Holness R., Dagher A., Trojanowski J.Q., Isacson O. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat. Med. 2008, 14:507-509.
193. Menegon A., Board P.G., Blackburn A.C., Mellick G.D., Le Couteur D.G. Parkinson's disease, pesticides, and glutathione transferase polymorphisms. Lancet 1998, 352:1344-1346.
194. Meredith G.E., Totterdell S., Petroske E., Santa Cruz K., Callison R.C., Lau Y.S. Lysosomal malfunction accompanies alpha-synuclein aggregation in a progressive mouse model of Parkinson's disease. Brain Res. 2002, 956:156-165.
195. Mergler D., Baldwin M. Early manifestations of manganese neurotoxicity in humans: an update. Environ. Res. 1997, 73:92-100.
196. Meulener M., Whitworth A.J., Armstrong-Gold C.E., Rizzu P., Heutink P., Wes P.D., Pallanck L.J., Bonini N.M. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr. Biol. 2005, 15:1572-1577.
197. Mizushima N., Levine B., Cuervo A.M., Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451:1069-1075.
198. Moore D.J., Zhang L., Dawson T.M., Dawson V.L. A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization. J. Neurochem. 2003, 87:1558-1567.
199. Moore D.J., Dawson V.L., Dawson T.M. Lessons from Drosophila models of DJ-1 deficiency. Sci. Aging Knowledge Environ. 2006, 2006:e2.
200. Morris M.E., Iansek R., Kirkwood B. A randomized controlled trial of movement strategies compared with exercise for people with Parkinson's disease. Mov. Disord. 2009, 24:64-71.
201. Mueller J.C., Fuchs J., Hofer A., Zimprich A., Lichtner P., Illig T., Berg D., Wullner U., Meitinger T., Gasser T. Multiple regions of alpha-synuclein are associated with Parkinson's disease. Ann. Neurol. 2005, 57:535-541.
202. Narendra D., Tanaka A., Suen D.F., Youle R.J. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J. Cell Biol. 2008, 183:795-803.
203. Narendra D.P., Jin S.M., Tanaka A., Suen D.F., Gautier C.A., Shen J., Cookson M.R., Youle R.J. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010, 8:e1000298.
204. Nayernouri T. Posttraumatic parkinsonism. Surg. Neurol. 1985, 24:263-264.
205. Ng C.H., Mok S.Z., Koh C., Ouyang X., Fivaz M.L., Tan E.K., Dawson V.L., Dawson T.M., Yu F., Lim K.L. Parkin protects against LRRK2 G2019S mutant-induced dopaminergic neurodegeneration in Drosophila. J. Neurosci. 2009, 29:11257-11262.
206. Nichols W.C., Pankratz N., Hernandez D., Paisan-Ruiz C., Jain S., Halter C.A., Michaels V.E., Reed T., Rudolph A., Shults C.W., Singleton A., Foroud T. Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease. Lancet 2005, 365:410-412.
207. Nieto M., Gil-Bea F.J., Dalfo E., Cuadrado M., Cabodevilla F., Sanchez B., Catena S., Sesma T., Ribe E., Ferrer I., Ramirez M.J., Gomez-Isla T. Increased sensitivity to MPTP in human alpha-synuclein A30P transgenic mice. Neurobiol. Aging 2006, 27:848-856.
208. Nishioka K., Ross O.A., Ishii K., Kachergus J.M., Ishiwata K., Kitagawa M., Kono S., Obi T., Mizoguchi K., Inoue Y., Imai H., Takanashi M., Mizuno Y., Farrer M.J., Hattori N. Expanding the clinical phenotype of SNCA duplication carriers. Mov. Disord. 2009, 24:1811-1819.
209. Norris E.H., Uryu K., Leight S., Giasson B.I., Trojanowski J.Q., Lee V.M. Pesticide exposure exacerbates alpha-synucleinopathy in an A53 T transgenic mouse model. Am. J. Pathol. 2007, 170:658-666.
210. Nuytemans K., Theuns J., Cruts M., Van Broeckhoven C. Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum. Mutat. 2010, 31:763-780.
211. Ogata A., Tashiro K., Nukuzuma S., Nagashima K., Hall W.W. A rat model of Parkinson's disease induced by Japanese encephalitis virus. J. Neurovirol. 1997, 3:141-147.
212. Ozelius L.J., Senthil G., Saunders-Pullman R., Ohmann E., Deligtisch A., Tagliati M., Hunt A.L., Klein C., Henick B., Hailpern S.M., Lipton R.B., Soto-Valencia J., Risch N., Bressman S.B. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N. Engl. J. Med. 2006, 354:424-425.
213. Paisan-Ruiz C., Jain S., Evans E.W., Gilks W.P., Simon J., van der Brug M., Lopez de Munain A., Aparicio S., Gil A.M., Khan N., Johnson J., Martinez J.R., Nicholl D., Carrera I.M., Pena A.S., de Silva R., Lees A., Marti-Masso J.F., Perez-Tur J., Wood N.W., Singleton A.B. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 2004, 44:595-600.
214. Paisan-Ruiz C., Washecka N., Nath P., Singleton A.B., Corder E.H. Parkinson's disease and low frequency alleles found together throughout LRRK2. Ann. Hum. Genet. 2009, 73:391-403.
215. Pals P., Lincoln S., Manning J., Heckman M., Skipper L., Hulihan M., Van den Broeck M., De Pooter T., Cras P., Crook J., Van Broeckhoven C., Farrer M.J. alpha-Synuclein promoter confers susceptibility to Parkinson's disease. Ann. Neurol. 2004, 56:591-595.
216. Pandey U.B., Nie Z., Batlevi Y., McCray B.A., Ritson G.P., Nedelsky N.B., Schwartz S.L., DiProspero N.A., Knight M.A., Schuldiner O., Padmanabhan R., Hild M., Berry D.L., Garza D., Hubbert C.C., Yao T.P., Baehrecke E.H., Taylor J.P. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 2007, 447:859-863.
217. Pankratz N., Wilk J.B., Latourelle J.C., DeStefano A.L., Halter C., Pugh E.W., Doheny K.F., Gusella J.F., Nichols W.C., Foroud T., Myers R.H. Genomewide association study for susceptibility genes contributing to familial Parkinson disease. Hum. Genet. 2009, 124:593-605.
218. Park J., Lee S.B., Lee S., Kim Y., Song S., Kim S., Bae E., Kim J., Shong M., Kim J.M., Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 2006, 441:1157-1161.
219. Pavese N., Khan N.L., Scherfler C., Cohen L., Brooks D.J., Wood N.W., Bhatia K.P., Quinn N.P., Lees A.J., Piccini P. Nigrostriatal dysfunction in homozygous and heterozygous parkin gene carriers: an 18F-DOPA PET progression study. Mov. Disord. 2009, 24:2260-2266.
220. Perez R.G., Hastings T.G. Could a loss of alpha-synuclein function put dopaminergic neurons at risk?. J. Neurochem. 2004, 89:1318-1324.
221. Perez F.A., Palmiter R.D. Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:2174-2179.
222. Petit A., Kawarai T., Paitel E., Sanjo N., Maj M., Scheid M., Chen F., Gu Y., Hasegawa H., Salehi-Rad S., Wang L., Rogaeva E., Fraser P., Robinson B., St George-Hyslop P., Tandon A. Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J. Biol. Chem. 2005, 280:34025-34032.
223. Piccini P., Burn D.J., Ceravolo R., Maraganore D., Brooks D.J. The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins. Ann. Neurol. 1999, 45:577-582.
224. Pienaar I.S., Gotz J., Feany M.B. Parkinson's disease: insights from non-traditional model organisms. Prog. Neurobiol. 2010, 92:558-571.
225. Plun-Favreau H., Hardy J. PINK1 in mitochondrial function. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:11041-11042.
226. Plun-Favreau H., Klupsch K., Moisoi N., Gandhi S., Kjaer S., Frith D., Harvey K., Deas E., Harvey R.J., McDonald N., Wood N.W., Martins L.M., Downward J. The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat. Cell Biol. 2007, 9:1243-1252.
227. Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., Lazzarini A.M., Duvoisin R.C., Di Iorio G., Golbe L.I., Nussbaum R.L. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997, 276:2045-2047.
228. Poole A.C., Thomas R.E., Andrews L.A., McBride H.M., Whitworth A.J., Pallanck L.J. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:1638-1643.
229. Powers K.M., Kay D.M., Factor S.A., Zabetian C.P., Higgins D.S., Samii A., Nutt J.G., Griffith A., Leis B., Roberts J.W., Martinez E.D., Montimurro J.S., Checkoway H., Payami H. Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Mov. Disord. 2008, 23:88-95.
230. Pramstaller P.P., Kis B., Eskelson C., Hedrich K., Scherer M., Schwinger E., Breakefield X.O., Kramer P.L., Ozelius L.J., Klein C. Phenotypic variability in a large kindred (Family LA) with deletions in the parkin gene. Mov. Disord. 2002, 17:424-426.
231. Pridgeon J.W., Olzmann J.A., Chin L.S., Li L. PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol. 2007, 5:e172.
232. Przedborski S., Levivier M., Jiang H., Ferreira M., Jackson-Lewis V., Donaldson D., Togasaki D.M. Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine. Neuroscience 1995, 67:631-647.
233. 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.
234. Qin L., Wu X., Block M.L., Liu Y., Breese G.R., Hong J.S., Knapp D.J., Crews F.T. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 2007, 55:453-462.
235. Rajput A.H., Uitti R.J. Paraquat and Parkinson's disease. Neurology 1987, 37:1820-1821.
236. Richfield E.K., Thiruchelvam M.J., Cory-Slechta D.A., Wuertzer C., Gainetdinov R.R., Caron M.G., Di Monte D.A., Federoff H.J. Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp. Neurol. 2002, 175:35-48.
237. Ritz B.R., Manthripragada A.D., Costello S., Lincoln S.J., Farrer M.J., Cockburn M., Bronstein J. Dopamine transporter genetic variants and pesticides in Parkinson's disease. Environ. Health Perspect. 2009, 117:964-969.
238. Rocca W.A., McDonnell S.K., Strain K.J., Bower J.H., Ahlskog J.E., Elbaz A., Schaid D.J., Maraganore D.M. Familial aggregation of Parkinson's disease: the Mayo Clinic family study. Ann. Neurol. 2004, 56:495-502.
239. Rochet J.C., Conway K.A., Lansbury P.T. Inhibition of fibrillization and accumulation of prefibrillar oligomers in mixtures of human and mouse alpha-synuclein. Biochemistry 2000, 39:10619-10626.
240. Rockenstein E., Mallory M., Hashimoto M., Song D., Shults C.W., Lang I., Masliah E. Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. J. Neurosci. Res. 2002, 68:568-578.
241. Ross C.A., Smith W.W. Gene-environment interactions in Parkinson's disease. Parkinsonism Relat. Disord. 2007, 13(Suppl. 3):S309-S315.
242. Ross O.A., Toft M., Whittle A.J., Johnson J.L., Papapetropoulos S., Mash D.C., Litvan I., Gordon M.F., Wszolek Z.K., Farrer M.J., Dickson D.W. Lrrk2 and Lewy body disease. Ann. Neurol. 2006, 59:388-393.
243. Saha S., Guillily M.D., Ferree A., Lanceta J., Chan D., Ghosh J., Hsu C.H., Segal L., Raghavan K., Matsumoto K., Hisamoto N., Kuwahara T., Iwatsubo T., Moore L., Goldstein L., Cookson M., Wolozin B. LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans. J. Neurosci. 2009, 29:9210-9218.
244. Sakaguchi-Nakashima A., Meir J.Y., Jin Y., Matsumoto K., Hisamoto N. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr. Biol. 2007, 17:592-598.
245. Sang T.K., Chang H.Y., Lawless G.M., Ratnaparkhi A., Mee L., Ackerson L.C., Maidment N.T., Krantz D.E., Jackson G.R. A Drosophila model of mutant human parkin-induced toxicity demonstrates selective loss of dopaminergic neurons and dependence on cellular dopamine. J. Neurosci. 2007, 27:981-992.
246. Satake W., Nakabayashi Y., Mizuta I., Hirota Y., Ito C., Kubo M., Kawaguchi T., Tsunoda T., Watanabe M., Takeda A., Tomiyama H., Nakashima K., Hasegawa K., Obata F., Yoshikawa T., Kawakami H., Sakoda S., Yamamoto M., Hattori N., Murata M., Nakamura Y., Toda T. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat. Genet. 2009, 41:1303-1307.
247. Sauer H., Oertel W.H. Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6-hydroxydopamine: a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 1994, 59:401-415.
248. Semchuk K.M., Love E.J., Lee R.G. Parkinson's disease and exposure to agricultural work and pesticide chemicals. Neurology 1992, 42:1328-1335.
249. Sherer T.B., Betarbet R., Stout A.K., Lund S., Baptista M., Panov A.V., Cookson M.R., Greenamyre J.T. An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J. Neurosci. 2002, 22:7006-7015.
250. 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.
251. Shimizu K., Ohtaki K., Matsubara K., Aoyama K., Uezono T., Saito O., Suno M., Ogawa K., Hayase N., Kimura K., Shiono H. Carrier-mediated processes in blood-brain barrier penetration and neural uptake of paraquat. Brain Res. 2001, 906:135-142.
252. Shimoji M., Zhang L., Mandir A.S., Dawson V.L., Dawson T.M. Absence of inclusion body formation in the MPTP mouse model of Parkinson's disease. Brain Res. Mol. Brain Res. 2005, 134:103-108.
253. Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 2000, 25:302-305.
254. Silvestri L., Caputo V., Bellacchio E., Atorino L., Dallapiccola B., Valente E.M., Casari G. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum. Mol. Genet. 2005, 14:3477-3492.
255. Simon-Sanchez J., Schulte C., Bras J.M., Sharma M., Gibbs J.R., Berg D., Paisan-Ruiz C., Lichtner P., Scholz S.W., Hernandez D.G., Kruger R., Federoff M., Klein C., Goate A., Perlmutter J., Bonin M., Nalls M.A., Illig T., Gieger C., Houlden H., Steffens M., Okun M.S., Racette B.A., Cookson M.R., Foote K.D., Fernandez H.H., Traynor B.J., Schreiber S., Arepalli S., Zonozi R., Gwinn K., van der Brug M., Lopez G., Chanock S.J., Schatzkin A., Park Y., Hollenbeck A., Gao J., Huang X., Wood N.W., Lorenz D., Deuschl G., Chen H., Riess O., Hardy J.A., Singleton A.B., Gasser T. Genome-wide association study reveals genetic risk underlying Parkinson's disease. Nat. Genet. 2009, 41:1308-1312.
256. Singleton A.B., 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 M.R., Muenter M., Baptista M., Miller D., Blancato J., Hardy J., Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003, 302:841.
257. Smith W.W., Pei Z., Jiang H., Dawson V.L., Dawson T.M., Ross C.A. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat. Neurosci. 2006, 9:1231-1233.
258. Spangenberg S., Hannerz H., Tuchsen F., Mikkelsen K.L. A nationwide population study of severe head injury and Parkinson's disease. Parkinsonism Relat. Disord. 2009, 15:12-14.
259. 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.
260. Sriram S.R., Li X., Ko H.S., Chung K.K., Wong E., Lim K.L., Dawson V.L., Dawson T.M. Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin. Hum. Mol. Genet. 2005, 14:2571-2586.
261. Stern M.B. Head trauma as a risk factor for Parkinson's disease. Mov. Disord. 1991, 6:95-97.
262. Sveinbjornsdottir S., Hicks A.A., Jonsson T., Petursson H., Gugmundsson G., Frigge M.L., Kong A., Gulcher J.R., Stefansson K. Familial aggregation of Parkinson's disease in Iceland. N. Engl. J. Med. 2000, 343:1765-1770.
263. Tan J.M., Wong E.S., Lim K.L. Protein misfolding and aggregation in Parkinson's disease. Antioxid. Redox Signal. 2009, 11:2119-2134.
264. Tan E.K., Kwok H.K., Tan L.C., Zhao W.T., Prakash K.M., Au W.L., Pavanni R., Ng Y.Y., Satake W., Zhao Y., Toda T., Liu J.J. Analysis of GWAS-linked loci in Parkinson disease reaffirms PARK16 as a susceptibility locus. Neurology 2010, 75:508-512.
265. Tanner C.M. Is the cause of Parkinson's disease environmental or hereditary? Evidence from twin studies. Adv. Neurol. 2003, 91:133-142.
266. Tanner C.M., Ottman R., Goldman S.M., Ellenberg J., Chan P., Mayeux R., Langston J.W. Parkinson disease in twins: an etiologic study. J. Am. Med. Assoc. 1999, 281:341-346.
267. Tao X., Tong L. Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease. J. Biol. Chem. 2003, 278:31372-31379.
268. Taylor C.A., Saint-Hilaire M.H., Cupples L.A., Thomas C.A., Burchard A.E., Feldman R.G., Myers R.H. Environmental, medical, and family history risk factors for Parkinson's disease: a New England-based case control study. Am. J. Med. Genet. 1999, 88:742-749.
269. Thiffault C., Langston J.W., Di Monte D.A. Increased striatal dopamine turnover following acute administration of rotenone to mice. Brain Res. 2000, 885:283-288.
270. Thiruchelvam M., Richfield E.K., Baggs R.B., Tank A.W., Cory-Slechta D.A. The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: implications for Parkinson's disease. J. Neurosci. 2000, 20:9207-9214.
271. Thiruchelvam M., Richfield E.K., Goodman B.M., Baggs R.B., Cory-Slechta D.A. Developmental exposure to the pesticides paraquat and maneb and the Parkinson's disease phenotype. Neurotoxicology 2002, 23:621-633.
272. Thiruchelvam M.J., Powers J.M., Cory-Slechta D.A., Richfield E.K. Risk factors for dopaminergic neuron loss in human alpha-synuclein transgenic mice. Eur. J. Neurosci. 2004, 19:845-854.
273. Tofaris G.K., Garcia Reitbock P., Humby T., Lambourne S.L., O'Connell M., Ghetti B., Gossage H., Emson P.C., Wilkinson L.S., Goedert M., Spillantini M.G. Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders. J. Neurosci. 2006, 26:3942-3950.
274. Tomas-Camardiel M., Rite I., Herrera A.J., de Pablos R.M., Cano J., Machado A., Venero J.L. Minocycline reduces the lipopolysaccharide-induced inflammatory reaction, peroxynitrite-mediated nitration of proteins, disruption of the blood-brain barrier, and damage in the nigral dopaminergic system. Neurobiol. Dis. 2004, 16:190-201.
275. Tomiyama H., Mizuta I., Li Y., Funayama M., Yoshino H., Li L., Murata M., Yamamoto M., Kubo S., Mizuno Y., Toda T., Hattori N. LRRK2 P755L variant in sporadic Parkinson's disease. J. Hum. Genet. 2008, 53:1012-1015.
276. Ton T.G., Heckbert S.R., Longstreth W.T., Rossing M.A., Kukull W.A., Franklin G.M., Swanson P.D., Smith-Weller T., Checkoway H. Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease. Mov. Disord. 2006, 21:964-969.
277. Tong Y., Shen J. alpha-Synuclein and LRRK2: partners in crime. Neuron 2009, 64:771-773.
278. Tong Y., Pisani A., Martella G., Karouani M., Yamaguchi H., Pothos E.N., Shen J. R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:14622-14627.
279. Tong Y., Yamaguchi H., Giaime E., Boyle S., Kopan R., Kelleher R.J., Shen J. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of {alpha}-synuclein, and apoptotic cell death in aged mice. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:9879-9884.
280. Troiano A.R., Elbaz A., Lohmann E., Belarbi S., Vidailhet M., Bonnet A.M., Lesage S., Pollak P., Cazeneuve C., Borg M., Feingold J., Durr A., Tazir M., Brice A. Low disease risk in relatives of North African lrrk2 Parkinson disease patients. Neurology 2010, 75:1118-1119.
281. Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol. 1968, 5:107-110.
282. Uversky V.N., Li J., Fink A.L. Pesticides directly accelerate the rate of alpha-synuclein fibril formation: a possible factor in Parkinson's disease. FEBS Lett. 2001, 500:105-108.
283. Valente E.M., Abou-Sleiman P.M., Caputo V., Muqit M.M., Harvey K., Gispert S., Ali Z., Del Turco D., Bentivoglio A.R., Healy D.G., Albanese A., Nussbaum R., Gonzalez-Maldonado R., Deller T., Salvi S., Cortelli P., Gilks W.P., Latchman D.S., Harvey R.J., Dallapiccola B., Auburger G., Wood N.W. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004, 304:1158-1160.
284. Vance J.M., Ali S., Bradley W.G., Singer C., Di Monte D.A. Gene-environment interactions in Parkinson's disease and other forms of parkinsonism. Neurotoxicology 2010, 31:598-602.
285. Venderova K., Kabbach G., Abdel-Messih E., Zhang Y., Parks R.J., Imai Y., Gehrke S., Ngsee J., Lavoie M.J., Slack R.S., Rao Y., Zhang Z., Lu B., Haque M.E., Park D.S. Leucine-rich repeat kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease. Hum. Mol. Genet. 2009, 18:4390-4404.
286. Vives-Bauza C., de Vries R.L., Tocilescu M., Przedborski S. PINK1/Parkin direct mitochondria to autophagy. Autophagy 2010, 6:315-316.
287. Vives-Bauza C., Zhou C., Huang Y., Cui M., de Vries R.L., Kim J., May J., Tocilescu M.A., Liu W., Ko H.S., Magrane J., Moore D.J., Dawson V.L., Grailhe R., Dawson T.M., Li C., Tieu K., Przedborski S. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:378-383.
288. Volles M.J., Lee S.J., Rochet J.C., Shtilerman M.D., Ding T.T., Kessler J.C., Lansbury P.T. Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry 2001, 40:7812-7819.
289. Wahner A.D., Sinsheimer J.S., Bronstein J.M., Ritz B. Inflammatory cytokine gene polymorphisms and increased risk of Parkinson disease. Arch. Neurol. 2007, 64:836-840.
290. Wang X.F., Li S., Chou A.P., Bronstein J.M. Inhibitory effects of pesticides on proteasome activity: implication in Parkinson's disease. Neurobiol. Dis. 2006, 23:198-205.
291. Wang C., Lu R., Ouyang X., Ho M.W., Chia W., Yu F., Lim K.L. Drosophila overexpressing parkin R275 W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities. J. Neurosci. 2007, 27:8563-8570.
292. Ward C.D., Duvoisin R.C., Ince S.E., Nutt J.D., Eldridge R., Calne D.B. Parkinson's disease in 65 pairs of twins and in a set of quadruplets. Neurology 1983, 33:815-824.
293. Weihofen A., Thomas K.J., Ostaszewski B.L., Cookson M.R., Selkoe D.J. Pink1 forms a multiprotein complex with Miro and Milton, linking Pink1 function to mitochondrial trafficking. Biochemistry 2009, 48:2045-2052.
294. Weisskopf M.G., O'Reilly E., Chen H., Schwarzschild M.A., Ascherio A. Plasma urate and risk of Parkinson's disease. Am. J. Epidemiol. 2007, 166:561-567.
295. West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., Dawson T.M. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:16842-16847.
296. West A.B., Moore D.J., Choi C., Andrabi S.A., Li X., Dikeman D., Biskup S., Zhang Z., Lim K.L., Dawson V.L., Dawson T.M. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum. Mol. Genet. 2007, 16:223-232.
297. Whitworth A.J., Theodore D.A., Greene J.C., Benes H., Wes P.D., Pallanck L.J. Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:8024-8029.
298. Williams D.B., Annegers J.F., Kokmen E., O'Brien P.C., Kurland L.T. Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism, and amyotrophic lateral sclerosis. Neurology 1991, 41:1554-1557.
299. Winkler S., Hagenah J., Lincoln S., Heckman M., Haugarvoll K., Lohmann-Hedrich K., Kostic V., Farrer M., Klein C. alpha-Synuclein and Parkinson disease susceptibility. Neurology 2007, 69:1745-1750.
300. Wirdefeldt K., Gatz M., Schalling M., Pedersen N.L. No evidence for heritability of Parkinson disease in Swedish twins. Neurology 2004, 63:305-311.
301. Wu X.F., Block M.L., Zhang W., Qin L., Wilson B., Zhang W.Q., Veronesi B., Hong J.S. The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxid. Redox Signal. 2005, 7:654-661.
302. Xiong H., Wang D., Chen L., Choo Y.S., Ma H., Tang C., Xia K., Jiang W., Ronai Z., Zhuang X., Zhang Z. Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation. J. Clin. Invest. 2009, 119:650-660.
303. Xiong Y., Coombes C.E., Kilaru A., Li X., Gitler A.D., Bowers W.J., Dawson V.L., Dawson T.M., Moore D.J. GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genet. 2010, 6:e1000902.
304. Xu Q., Park Y., Huang X., Hollenbeck A., Blair A., Schatzkin A., Chen H. Physical activities and future risk of Parkinson disease. Neurology 2010, 75:341-348.
305. Yamada M., Iwatsubo T., Mizuno Y., Mochizuki H. Overexpression of alpha-synuclein in rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. J. Neurochem. 2004, 91:451-461.
306. Yang Y., Gehrke S., Haque M.E., Imai Y., Kosek J., Yang L., Beal M.F., Nishimura I., Wakamatsu K., Ito S., Takahashi R., Lu B. Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:13670-13675.
307. Yang Y., Ouyang Y., Yang L., Beal M.F., McQuibban A., Vogel H., Lu B. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:7070-7075.
308. Yao D., Gu Z., Nakamura T., Shi Z.Q., Ma Y., Gaston B., Palmer L.A., Rockenstein E.M., Zhang Z., Masliah E., Uehara T., Lipton S.A. Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc. Natl. Acad. Sci. U.S.A. 2004, 101:10810-10814.
309. Yumino K., Kawakami I., Tamura M., Hayashi T., Nakamura M. Paraquat- and diquat-induced oxygen radical generation and lipid peroxidation in rat brain microsomes. J. Biochem. 2002, 131:565-570.
310. Zarranz J.J., Alegre J., Gomez-Esteban J.C., Lezcano E., Ros R., Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atares B., Llorens V., Gomez Tortosa E., del Ser T., Munoz D.G., de Yebenes J.G. The new mutation, E46 K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 2004, 55:164-173.
311. Zhang Y., Gao J., Chung K.K., Huang H., Dawson V.L., Dawson T.M. Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:13354-13359.
312. Zhang L., Shimoji M., Thomas B., Moore D.J., Yu S.W., Marupudi N.I., Torp R., Torgner I.A., Ottersen O.P., Dawson T.M., Dawson V.L. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum. Mol. Genet. 2005, 14:2063-2073.
313. Zhang Z., Burgunder J.M., An X., Wu Y., Chen W., Zhang J., Wang Y., Xu Y., Gou Y., Yuan G., Mao X., Peng R. LRRK2 R1628P variant is a risk factor of Parkinson's disease among Han-Chinese from mainland China. Mov. Disord. 2009, 24:1902-1905.
314. Zhou C., Huang Y., Shao Y., May J., Prou D., Perier C., Dauer W., Schon E.A., Przedborski S. The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc. Natl. Acad. Sci. U.S.A. 2008, 105:12022-12027.
315. Zigmond M.J., Cameron J.L., Leak R.K., Mirnics K., Russell V.A., Smeyne R.J., Smith A.D. Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. Parkinsonism Relat. Disord. 2009, 15(Suppl. 3):S42-S45.
316. Zimprich A., Biskup S., Leitner P., Lichtner P., Farrer M., Lincoln S., Kachergus J., Hulihan M., Uitti R.J., Calne D.B., Stoessl A.J., Pfeiffer R.F., Patenge N., Carbajal I.C., Vieregge P., Asmus F., Muller-Myhsok B., Dickson D.W., Meitinger T., Strom T.M., Wszolek Z.K., Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004, 44:601-607.