Pathogenic mutations in Parkinson disease

Human Mutation

Volumn 28, Issue 7, 2007, Pages 641-653

  Tan, Eng King ^a   Skipper, Lisa M ^b  

^a SINGAPORE GENERAL HOSPITAL   (Singapore)

^b MAYO CLINIC   (United States)

Author keywords

Familial; Gene; Mutation; Neurodegeneration; Parkinson disease; PD; Sporadic

Indexed keywords

ALPHA SYNUCLEIN; PARKIN; PHOSPHATASE AND TENSIN INDUCED KINASE 1; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEASOME; PROTEIN SERINE THREONINE KINASE; UBIQUITIN; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

DEGENERATIVE DISEASE; DISEASE CARRIER; DOPAMINERGIC SYSTEM; ENVIRONMENTAL FACTOR; ETHNIC GROUP; FAMILIAL DISEASE; GENE DOSAGE; GENE MUTATION; GENETIC MARKER; HUMAN; NEUROLOGIC DISEASE; PARKINSON DISEASE; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

ALPHA-SYNUCLEIN; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MUTATION; ONCOGENE PROTEINS; PARKINSON DISEASE; PROTEIN KINASES; PROTEIN-SERINE-THREONINE KINASES; UBIQUITIN THIOLESTERASE; UBIQUITIN-PROTEIN LIGASES;

EID: 34447289622     PISSN: 10597794     EISSN: None     Source Type: Journal    
DOI: 10.1002/humu.20507     Document Type: Review

References (174)

1. Abeliovich A, Schmitz Y, Farinas I, Choi-Lundberg D, Ho WH, Castillo PE, Shinsky N, Verdugo JM, Armanini M, Ryan A, Hynes M, Phillips H, Sulzer D, Rosenthal A. 2000. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25:239-252.
2. Abou-Sleiman PM, Muqit MM, McDonald NQ, Yang YX, Gandhi S, Healy DG, Harvey K, Harvey RJ, Deas E, Bhatia K, Quinn N, Lees A, Latchman DS, Wood NW. 2006. Heterozygous effect for PINK1 mutations in Parkinson's disease? Ann Neurol 60:414-419.
3. Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, Pittman AM, Lashley T, Canet-Aviles R, Miller DW, McLendon C, Strand C, Leonard AJ, Abou-Sleiman PM, Healy DG, Ariga H, Wood NW, de Silva R, Revesz T, Hardy JA, Lees AJ. 2004. The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease. Brain 127(Pt 2):420-430.
4. Berg D, Niwar M, Maass S, Zimprich A, Moller JC, Wuellner U, Schmitz-Hubsch T, Klein C, Tan EK, Schols L, Marsh L, Dawson TM, Janetzky B, Muller T, Woitalla D, Kostic V, Pramstaller PP, Oertel WH, Bauer P, Krueger R, Gasser T, Riess O. 2005. Alpha-synuclein and Parkinson's disease: implications from the screening of more than 1,900 patients. Mov Disord 20:1191-1194.
5. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P. 2003. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256-259.
6. Bonifati V. 2005. Genetics of Parkinson's disease. Minerva Med 96: 175-186.
7. Brown TP, Rumsby PC, Capleton AC, Rushton L, Levy LS. 2006. Pesticides and Parkinson's disease - is there a link? Environ Health Perspect 114: 156-164.
8. Cabin DE, Shimazu K, Murphy D, Cole NB, Gottschalk W, McIlwain KL, Orrison B, Chen A, Ellis CE, Paylor R, Lu B, Nussbaum RL. 2002. Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J Neurosci 22:8797-8807.
9. Canet-Aviles RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR. 2004. The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci USA 101:9103-9108.
10. Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, Levecque C, Larvor L, Andrieux J, Hulihan M, Waucquier N, Defebvre L, Amouyel P, Farrer M, Destee A. 2004. Alpha-synuclein locus duplication as a cause of familial Parkinson's disease. Lancet 364: 1167-1169.
11. Chen L, Feany MB. 2005. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci 8:657-663.
12. Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, Gearing M, Levey AI, Chin LS, Li L. 2006. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem 281: 10816-10824.
13. Clark LN, Afridi S, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Singleton A, Wavrant De-Vrieze F, Hardy J, Mayeux R, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. 2004. Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations. Mov Disord 19:796-800.
14. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. 2006a. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441:1162-1166.
15. Clark LN, Afridi S, Karlins E, Wang Y, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. 2006b. Case-control study of the parkin gene in early-onset Parkinson disease. Arch Neurol 63:548-552.
16. Clayton DF, George JM. 1998. The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci 21:249-254.
17. Conway KA, Harper JD, Lansbury PT. 1998. Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med 4:1318-1320.
18. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr. 2000. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA 97:571-576.
19. Cookson MR, Lockhart PJ, McLendon C, O'Farrell C, Schlossmacher M, Farrer MJ. 2003. RING finger 1 mutations in Parkin produce altered localization of the protein. Hum Mol Genet 12:2957-2965.
20. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, Cao S, Caldwell KA, Caldwell GA, Marsischky G, Kolodner RD, Labaer J, Rochet JC, Bonini NM, Lindquist S. 2006. Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313: 324-328.
21. Corti O, Hampe C, Koutnikova H, Darios F, Jacquier S, Prigent A, Robinson JC, Pradier L, Ruberg M, Mirande M, Hirsch E, Rooney T, Fournier A, Brice A. 2003. The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration. Hum Mol Genet 12:1427-1437.
22. Darios F, Corti O, Lucking CB, Hampe C, Muriel MP, Abbas N, Gu WJ, Hirsch EC, Rooney T, Ruberg M, Brice A. 2003. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 12:517-526.
23. Dawson TM, Dawson VL. 2003. Molecular pathways of neurodegeneration in Parkinson's disease. Science 302:819-822.
24. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, Fratiglioni L, Lobo A, Martinez-Lage J, Trenkwalder C, Hofman A. 2000. Prevalence of Parkinson's disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54(Suppl 5):S21-S23.
25. Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V, Italian Parkinson Genetics Network. 2005. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 365:412-415.
26. Di Fonzo A, Wu-Chou YH, Lu CS, van Doeselaar M, Simons EJ, Rohe CF, Chang HC, Chen RS, Weng YH, Vanacore N, Breedveld GJ, Oostra BA, Bonifati V. 2006. A common missense variant in the LRRK2 gene, Gly2385Arg, associated with Parkinson's disease risk in Taiwan. Neurogenetics 7:133-138.
27. Farrer M, Chan P, Chen R, Tan L, Lincoln S, Hernandez D, Forno L, Gwinn-Hardy K, Petrucelli L, Hussey J, Singleton A, Tanner C, Hardy J, Langston JW. 2001. Lewy bodies and parkinsonism in families with parkin mutations. Ann Neurol 50:293-300.
28. Farrer M, Kachergus J, Forno L, Lincoln S, Wang DS, Hulihan M, Maraganore D, Gwinn-Hardy K, Wszolek Z, Dickson D, Langston JW. 2004. Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann Neurol 55:174-179.
29. Farrer M, Stone J, Mata IF, Lincoln S, Kachergus J, Hulihan M, Strain KJ, Maraganore DM. 2005. LRRK2 mutations in Parkinson disease. Neurology 65:738-740.
30. Fleming SM, Salcedo J, Fernagut PO, Rockenstein E, Masliah E, Levine MS, Chesselet MF. 2004. Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. J Neurosci 24: 9434-9940.
31. Fortin DL, Troyer MD, Nakamura K, Kubo S, Anthony MD, Edwards RH. 2004. Lipid rafts mediate the synaptic localization of alpha-synuclein. J Neurosci 24:6715-6723.
32. Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C, Shults C, Marder K, Conneally PM, Nichols WC, Parkinson Study Group. 2003. Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology 60:796-801.
33. Fung HC, Chen CM, Hardy J, Hernandez D, Singleton A, Wu YR. 2006. Lack of G2019S LRRK2 mutation in a cohort of Taiwanese with sporadic Parkinson's disease. Mov Disord 21:880-881.
34. Gandhi S, Muqit MM, Stanyer L, Healy DG, Ahou-Sleiman PM, Hargreaves I, Heales S, Ganguly M, Parsons L, Lees AJ, Latchman DS, Holton JL, Wood NW, Revesz T. 2006. PINK1 protein in normal human brain and Parkinson's disease. Brain 129(Pt 7):1720-1731.
35. Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW. 2005. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365:415-416.
36. Gispert S, Trenkwalder C, Mota-Vieira L, Kostic V, Auburger G. 2005. Failure to find alpha-synuclein gene dosage changes in 190 patients with familial Parkinson disease. Arch Neurol 62:96-98.
37. Gloeckner CJ, Kinkl N, Schumacher A, Braun RJ, O'Neill E, Meitinger T, Kolch W, Prokisch H, Ueffing M. 2006. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Genet 15:223-232.
38. Goldberg MS, Fleming SM, Palacino JJ, Cepeda C, Lam HA, Bhatnagar A, Meloni EG, Wu N, Ackerson LC, Klapstein GJ, Gajendiran M, Roth BL, Chesselet MF, Maidment NT, Levine MS, Shen J. 2003. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem 278:43628-43635.
39. Goldberg MS, Pisani A, Haburcak M, Vortherms TA, Kitada T, Costa C, Tong Y, Martella G, Tscherter A, Martins A, Bernardi G, Roth BL, Pothos EN, Calabresi P, Shen J. 2005. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45:489-496.
40. Greenbaum EA, Graves CL, Mishizen-Eberz AJ, Lupoli MA, Lynch DR, Englander SW, Axelsen PH, Giasson BI. 2005. The E46K mutation in alpha-synuclein increases amyloid fibril formation. J Biol Chem 280: 7800-7807.
41. Greene JC, Whitworth AJ, Kuo I, Andrews LA, Feany MB, Pallanck LJ. 2003. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci USA 100:4078-4083.
42. Gu WJ, Corti O, Araujo F, Hampe C, Jacquier S, Lucking CB, Abbas N, Duyckaerts C, Rooney T, Pradier L, Ruberg M, Brice A. 2003. The C289G and C418R missense mutations cause rapid sequestration of human Parkin into insoluble aggregates. Neurobiol Dis 14:357-364.
43. Hasegawa T, Matsuzaki-Kobayashi M, Takeda A, Sugeno N, Kikuchi A, Furukawa K, Perry G, Smith MA, Itoyama Y. 2006. Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: implications for selective neurodegeneration in Parkinson's disease. FEBS Lett 580: 2147-2152.
44. Hatano Y, Li Y, Sato K, Asakawa S, Yamamura Y, Tomiyama H, Yoshino H, Asahina M, Kobayashi S, Hassin-Baer S, Lu CS, Ng AR, Rosales RL, Shimizu N, Toda T, Mizuno Y, Hattori N. 2004. Novel PINK1 mutations in early-onset parkinsonism. Ann Neurol 56:424-427.
45. Haugarvoll K, Wszolek ZK. 2006. PARK8 LRRK2 parkinsonism. Curr Neurol Neurosci Rep 6:287-294.
46. Healy DG, Abou-Sleiman PM, Gibson JM, Ross OA, Jain S, Gandhi S, Gosal D, Muqit MM, Wood NW, Lynch T. 2004. PINK1 (PARK6) associated Parkinson disease in Ireland. Neurology 26;63:1486-1488.
47. Healy DG, Abou-Sleiman PM, Casas JP, Ahmadi KR, Lynch T, Gandhi S, Muqit MM, Foltynie T, Barker R, Bhatia KP, Quinn NP, Lees AJ, Gibson JM, Holton JL, Revesz T, Goldstein DB, Wood NW. 2006. UCHL-1 is not a Parkinson's disease susceptibility gene. Ann Neurol 59:627-633.
48. Hering R, Strauss KM, Tao X, Bauer A, Woitalla D, Mietz EM, Petrovic S, Bauer P, Schaible W, Muller T, Schols L, Klein C, Berg D, Meyer PT, Schulz JB, Wollnik B, Tong L, Kruger R, Riess O. 2004. Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7). Hum Mutat 24:321-329.
49. Hernandez DG, Paisan-Ruiz C, McInerney-Leo A, Jain S, Meyer-Lindenberg A, Evans EW, Berman KF, Johnson J, Auburger G, Schaffer AA, Lopez GJ, Nussbaum RL, Singleton AB. 2005. Clinical and positron emission tomography of Parkinson's disease caused by LRRK2. Ann Neurol 57:453-456.
50. Hiller A, Hagenah JM, Djarmati A, Hedrich K, Reetz K, Schneider-Gold C, Kress W, Munchau A, Klein C. 2007. Phenotypic spectrum of PINK1-associated parkinsonism in 15 mutation carriers from 1 family. Mov Disord 22:145-147.
51. Ibanez P, Bonnet AM, Debarges B, Lohmann E, Tison F, Pollak P, Agid Y, Durr A, Brice A. 2004. Causal relation between alpha-synuclein gene duplication and familial Parkinson's disease. Lancet. 364: 1169-1171.
52. Ibanez P, Lesage S, Lohmann E, Thobois S, De Michele G, Borg M, Agid Y, Durr A, Brice A. 2006. Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa. Brain 129(Pt 3): 686-694.
53. Itier JM, Ibanez P, Mena MA, Abbas N, Cohen-Salmon C, Bohme GA, Laville M, Pratt J, Corti O, Pradier L, Ret G, Joubert C, Periquet M, Araujo F, Negroni J, Casarejos MJ, Canals S, Solano R, Serrano A, Gallego E, Sanchez M, Denefle P, Benavides J, Tremp G, Rooney TA, Brice A, Garcia de Yebenes J. 2003. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12:2277-2291.
54. Johnson J, Hague SM, Hanson M, Gibson A, Wilson KE, Evans EW, Singleton AA, McInerney-Leo A, Nussbaum RL, Hernandez DG, Gallardo M, McKeith IG, Burn DJ, Ryu M, Hellstrom O, Ravina B, Eerola J, Perry RH, Jaros E, Tienari P, Weiser R, Gwinn-Hardy K, Morris CM, Hardy J, Singleton AB. 2004. SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies. Neurology 63:554-556.
55. Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J, Gibson JM, Ross OA, Lynch T, Wiley J, Payami H, Nutt J, Maraganore DM, Czyzewski K, Styczynka M, Wszolek ZK, Farrer MJ, Toft M. 2005. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet 76:672-680.
56. Kann M, Jacobs H, Mohrmann K, Schumacher K, Hedrich K, Garrels J, Wiegers K, Schwinger E, Pramstaller PP, Breakefield XO, Ozelius LJ, Vieregge P, Klein C. 2002. Role of parkin mutations in 111 community-based patients with early-onset parkinsonism. Ann Neurol 51: 621-625.
57. Kay DM, Kramer P, Higgins D, Zabetian CP, Payami H. 2005. Escaping Parkinson's disease: a neurologically healthy octogenarian with the LRRK2 G2019S mutation. Mov Disord 20:1077-1078.
58. Khan NL, Brooks DJ, Pavese N, Sweeney MG, Wood NW, Lees AJ, Piccini P. 2002a. Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study. Brain 125(Pt 10):2248-2256.
59. Khan NL, Valente EM, Bentivoglio AR, Wood NW, Albanese A, Brooks DJ, Piccini P. 2002b. Clinical and subclinical dopaminergic dysfunction in PARK6-linked parkinsonism: an 18F-dopa PET study. Ann Neurol 52:849-853.
60. Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, Bhatia KP, Quinn N. 2003. Parkin disease: a phenotypic study of a large case series. Brain 126(Pt 6):1279-1292.
61. Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A, You-Ten AJ, Kalia SK, Horne P, Westaway D, Lozano AM, Anisman H, Park DS, Mak TW. 2005. Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci USA 102:5215-5220.
62. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. 1998. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605-608.
63. Ko HS, von Coelln R, Sriram SR, Kim SW, Chung KK, Pletnikova O, Troncoso J, Johnson B, Saffary R, Goh EL, Song H, Park BJ, Kim MJ, Kim S, Dawson VL, Dawson TM. 2005. Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J Neurosci 25:7968-7978.
64. Korr D, Toschi L, Donner P, Pohlenz HD, Kreft B, Weiss B. 2006. LRRK1 protein kinase activity is stimulated upon binding of GTP to its Roc domain. Cell Signal 18:910-920.
65. Kruger R, Kuhn W, Muller T, Woitalla D, Graeber M, Kosel S, Przuntek H, Epplen JT, Schols L, Riess O. 1998. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet 18:106-108.
66. Kubo SI, Kitami T, Noda S, Shimura H, Uchiyama Y, Asakawa S, Minoshima S, Shimizu N, Mizuno Y, Hattori N. 2001. Parkin is associated with cellular vesicles. J Neurochem 78:42-54.
67. Langston JW, Ballard P, Tetrud JW, Irwin I. 1983. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979-980.
68. Lashuel HA, Petre BM, Wall J, Simon M, Nowak RJ, Walz T, Lansbury PT Jr. 2002. Alpha-synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol 322: 1089-1102.
69. Lazzarini AM, Myers RH, Zimmerman TR Jr, Mark MH, Golbe LI, Sage JI, Johnson WG, Duvoisin RC. 1994. A clinical genetic study of Parkinson's disease: evidence for dominant transmission. Neurology 44(Pt 1): 499-506.
70. Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK. 2003. Mutations in NR4A2 associated with familial Parkinson disease. Nat Genet 33:85-89.
71. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH. 1998. The ubiquitin pathway in Parkinson's disease. Nature 395:451-452.
72. Lesage S, Leutenegger AL, Ibanez P, Janin S, Lohmann E, Durr A, Brice A, French Parkinson's Disease Genetics Study Group. 2005. LRRK2 haplotype analyses in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century. Am J Hum Genet 77:330-332.
73. Lesage S, Durr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A. 2006. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med 354:422-423.
74. Li Y, Tomiyama H, Sato K, Hatano Y, Yoshino H, Atsumi M, Kitaguchi M, Sasaki S, Kawaguchi S, Miyajima H, Toda T, Mizuno Y, Hattori N. 2005. Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism. Neurology 64:1955-1957.
75. Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. 2002. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell 111: 209-218.
76. Lockhart PJ, Lincoln S, Hulihan M, Kachergus J, Wilkes K, Bisceglio G, Mash DC, Farrer MJ. 2004. DJ-1 mutations are a rare cause of recessively inherited early onset parkinsonism mediated by loss of protein function. J Med Genet 41:e22.
77. Lohmann E, Periquet M, Bonifati V, Wood NW, De Michele G, Bonnet AM, Fraix V, Broussolle E, Horstink MW, Vidailhet M, Verpillat P, Gasser T, Nicholl D, Teive H, Raskin S, Rascol O, Destee A, Ruberg M, Gasparini F, Meco G, Agid Y, Durr A, Brice A, French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. 2003. How much phenotypic variation can be attributed to parkin genotype? Ann Neurol 54:176-185.
78. Lowe J, McDermott H, Landon M, Mayer RJ, Wilkinson KD. 1990. Ubiquitin carboxyl-terminal hydrolase (PGP 9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative diseases. J Pathol 161:153-160.
79. Lu CS, Simons EJ, Wu-Chou YH, Fonzo AD, Chang HC, Chen RS, Weng YH, Rohe CF, Breedveld GJ, Hattori N, Gasser T, Oostra BA, Bonifati V. 2005. The LRRK2 I2012T G2019S, and I2020T mutations are rare in Taiwanese patients with sporadic Parkinson's disease. Parkinsonism Relat Disord 11:521-522.
80. Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A, French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. 2000. Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med 342:1560-1567.
81. Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Kruger R, Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, de Andrade M, Rocca WA, UCHL1 Global Genetics Consortium. 2004. UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol 55:512-521.
82. Maraganore DM, de Andrade M, Elbaz A, Farrer MJ, Ioannidis JP, Kruger R, Rocca WA, Schneider NK, Lesnick TG, Lincoln SJ, Hulihan MM, Aasly JO, Ashizawa T, Chartier-Harlin MC, Checkoway H, Ferrarese C, Hadjigeorgiou G, Hattori N, Kawakami H, Lambert JC, Lynch T, Mellick GD, Papapetropoulos S, Parsian A, Quattrone A, Riess O, Tan EK, Van Broeckhoven C, Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium. 2006. Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. JAMA 296:661-670.
83. Marder K, Tang MX, Mejia H, Alfaro B, Cote L, Louis E, Groves J, Mayeux R. 1996. Risk of Parkinson's disease among first-degree relatives: a community-based study. Neurology 47:155-160.
84. Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schols L, Schulz JB, Riess O, Kruger R. 2003. Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet 12:1223-1231.
85. Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L. 2000. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287:1265-1269.
86. Mata IF, Lockhart PJ, Farrer MJ. 2004. Parkin genetics: one model for Parkinson's disease. Hum Mol Genet 13(Spec No 1):R127-R33.
87. Mata IF, Taylor JP, Kachergus J, Hulihan M, Huerta C, Lahoz C, Blazquez M, Guisasola LM, Salvador C, Ribacoba R, Martinez C, Farrer M, Alvarez V. 2005. LRRK2 R1441G in Spanish patients with Parkinson's disease. Neurosci Lett 382:309-311.
88. Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. 2006. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci 29:286-293.
89. Matsuda N, Kitami T, Suzuki T, Mizuno Y, Hattori N, Tanaka K. 2006. Diverse effects of pathogenic mutations of Parkin that catalyze multiple monoubiquitylation in vitro. J Biol Chem 281:3204-3209.
90. Melrose HL, Lincoln SJ, Tyndall GM, Farrer MJ. 2006. Parkinson's disease: a rethink of rodent models. Exp Brain Res 173:196-204.
91. Meulener M, Whitworth AJ, Armstrong-Gold CE, Rizzu P, Heutink P, Wes PD, Pallanck LJ, Bonini NM. 2005. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr Biol 15:1572-1577.
92. Miller DW, Ahmad R, Hague S, Baptista MJ, Canet-Aviles R, McLendon C, Carter DM, Zhu PP, Stadler J, Chandran J, Klinefelter GR, Blackstone C, Cookson MR. 2003. L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system. J Biol Chem 278:36588-36595.
93. Miller DW, Hague SM, Clarimon J, Baptista M, Gwinn-Hardy K, Cookson MR, Singleton AB. 2004. Alpha-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology 62: 1835-1838.
94. Mitsumoto A, Nakagawa Y. 2001. DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin. Free Radic Res 35: 885-893.
95. Moore DJ, Zhang L, Dawson TM, Dawson VL. 2003. A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization. J Neurochem 87: 1558-1567.
96. Mouatt-Prigent A, Muriel MP, Gu WJ, El Hachimi KH, Lucking CB, Brice A, Hirsch EC. 2004. Ultrastructural localization of parkin in the rat brainstem, thalamus and basal ganglia. J Neural Transm 111:1209-1218.
97. Munhoz RP, Sa DS, Rogaeva E, Salehi-Rad S, Sato C, Medeiros H, Farrer M, Lang AE. 2004. Clinical findings in a large family with a parkin ex3delta40 mutation. Arch Neurol 461:701-704.
98. Murphy DD, Rueter SM, Trojanowski JQ, Lee VM. 2000. Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J Neurosci 20:3214-3220.
99. Nishikawa K, Li H, Kawamura R, Osaka H, Wang YL, Hara Y, Hirokawa T, Manago Y, Amano T, Noda M, Aoki S, Wada K. 2003. Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. Biochem Biophys Res Commun 304:176-183.
100. Nishioka K, Hayashi S, Farrer MJ, Singleton AB, Yoshino H, Imai H, Kitami T, Sato K, Kuroda R, Tomiyama H, Mizoguchi K, Murata M, Toda T, Imoto I, Inazawa J, Mizuno Y, Hattori N. 2006. Clinical heterogeneity of alpha-synuclein gene duplication in Parkinson's disease. Ann Neurol 59:298-309.
101. Oliveri RL, Zappia M, Annesi G, Bosco D, Annesi F, Spadafora P, Pasqua AA, Tomaino C, Nicoletti G, Pirritano D, Labate A, Gambardella A, Logroscino G, Manobianca G, Epifanio A, Morgante L, Savettieri G, Quattrone A. 2001. The parkin gene is not involved in late-onset Parkinson's disease. Neurology 57:359-362.
102. Olzmann JA, Brown K, Wilkinson KD, Rees HD, Huai Q, Ke H, Levey AI, Li L, Chin LS. 2004. Familial Parkinson's disease-associated L166P mutation disrupts DJ-1 protein folding and function. J Biol Chem 279: 8506-8515.
103. Osaka H, Wang YL, Takada K, Takizawa S, Setsuie R, Li H, Sato Y, Nishikawa K, Sun YJ, Sakurai M, Harada T, Hara Y, Kimura I, Chiba S, Namikawa K, Kiyama H, Noda M, Aoki S, Wada K. 2003. Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet 12:1945-1958.
104. Outeiro TF, Lindquist S. 2003. Yeast cells provide insight into alpha-synuclein biology and pathobiology. Science 302:1772-1775.
105. Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM, Lipton RB, Soto-Valencia J, Risch N, Bressman SB. 2006. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med 354:424-425.
106. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB. 2004. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44:595-600.
107. Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J. 2004. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279:18614-18622.
108. Pals P, Lincoln S, Manning J, Heckman M, Skipper L, Hulihan M, Van den Broeck M, De Pooter T, Cras P, Crook J, and others. 2004. Alpha-synuclein promoter confers susceptibility to Parkinson's disease. Ann Neurol 56:591-595.
109. Pandey N, Schmidt RE, Galvin JE. 2006. The alpha-synuclein mutation E46K promotes aggregation in cultured cells. Exp Neurol 197:515-520.
110. Periquet M, Latouche M, Lohmann E, Rawal N, De Michele G, Ricard S, Teive H, Fraix V, Vidailhet M, Nicholl D, Barone P, Wood NW, Raskin S, Deleuze JF, Agid Y, Durr A, Brice A, French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. 2003. Parkin mutations are frequent in patients with isolated early-onset Parkinsonism. Brain 126(Pt 6):1271-1278.
111. Pesah Y, Pham T, Burgess H, Middlebrooks B, Verstreken P, Zhou Y, Harding M, Bellen H, Mardon G. 2004. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 131:2183-2194.
112. 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. 2005. Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. J Biol Chem 280:34025-34032.
113. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. 1997. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276:2045-2047.
114. Pramstaller PP, Schlossmacher MG, Jacques TS, Scaravilli F, Eskelson C, Pepivani I, Hedrich K, Adel S, Gonzales-McNeal M, Hilker R, Kramer PL, Klein C. 2005. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol 58:411-422.
115. Ramirez A, Heimbach A, Grundemann J, Stiller B, Hampshire D, Cid LP, Goebel I, Mubaidin AF, Wriekat AL, Roeper J, Al-Din A, Hillmer AM, Karsak M, Liss B, Woods CG, Behrens MI, Kubisch C. 2006. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 38:1184-1191.
116. Ren Y, Zhao J, Feng J. 2003. Parkin binds to alpha/beta tubulin and increases their ubiquitination and degradation. J Neurosci 23: 3316-3324.
117. Rockenstein E, Mallory M, Hashimoto M, Song D, Shults CW, Lang I, Masliah E. 2002. Differential neuropathological alterations in transgenic mice expressing alpha-synuclein from the platelet-derived growth factor and Thy-1 promoters. J Neurosci Res 68:568-578.
118. Rohe CF, Montagna P, Breedveld G, Cortelli P, Oostra BA, Bonifati V. 2004. Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism. Ann Neurol 56:427-431.
119. Saigoh K, Wang YL, Suh JG, Yamanishi T, Sakai Y, Kiyosawa H, Harada T, Ichihara N, Wakana S, Kikuchi T, Wada K. 1999. Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice. Nat Genet 23:47-51.
120. Schlossmacher MG, Frosch MP, Gai WP, Medina M, Sharma N, Forno L, Ochiishi T, Shimura H, Sharon R, Hattori N, Langston JW, Mizuno Y, Hyman BT, Selkoe DJ, Kosik KS. 2002. Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am J Pathol 160:1655-1667.
121. Shimura H, Hattori N, Kubo S, Yoshikawa M, Kitada T, Matsumine H, Asakawa S, Minoshima S, Yamamura Y, Shimizu N, Mizuno Y. 1999. Immunohistochemical and subcellular localization of Parkin protein: absence of protein in autosomal recessive juvenile parkinsonism patients. Ann Neurol 45:668-672.
122. Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. 2000. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302-305.
123. Shimura H, Schlossmacher MG, Hattori N, Frosch MP, Trockenbacher A, Schneider R, Mizuno Y, Kosik KS, Selkoe DJ. 2001. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science 293:263-269.
124. Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G. 2005. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14: 3477-3492.
125. Skipper L, Shen H, Chua E, Bonnard C, Kolatkar P, Tan LC, Jamora RD, Puvan K, Puong KY, Zhao Y, Pavanni R, Wong MC, Yuen Y, Farrer M, Liu JJ, Tan EK. 2005a. Analysis of LRRK2 functional domains in nondominant Parkinson disease. Neurology 65:1319-1321.
126. Skipper L, Li Y, Bonnard C, Pavanni R, Yih Y, Chua E, Sung WK, Tan L, Wong MC, Tan EK, Liu J. 2005b. Comprehensive evaluation of common genetic variation within LRRK2 reveals evidence for association with sporadic Parkinson's disease. Hum Mol Genet 14:3549-3556.
127. Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, Dawson VL, Dawson TM, Ross CA. 2005. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci USA 102:18676-18681.
128. Specht CG, Schoepfer R. 2001. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 2:11.
129. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. 1997. Alpha-synuclein in Lewy bodies. Nature 388:839-840.
130. Stenmark H, Olkkonen VM. 2001. The Rab GTPase family. Genome Biol 2:REVIEWS3007.
131. Strauss KM, Martins LM, Plun-Favreau H, Marx FP, Kautzmann S, Berg D, Gasser T, Wszolek Z, Muller T, Bornemann A, Wolburg H, Downward J, Riess O, Schulz JB, Kruger R. 2005. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet 14: 2099-2111.
132. Sun M, Latourelle JC, Wooten GF, Lew MF, Klein C, Shill HA, Golbe LI, Mark MH, Racette BA, Perlmutter JS, Parsian A, Guttman M, Nicholson G, Xu G, Wilk JB, Saint-Hilaire MH, DeStefano AL, Prakash R, Williamson S, Suchowersky O, Labelle N, Growdon JH, Singer C, Watts RL, Goldwurm S, Pezzoli G, Baker KB, Pramstaller PP, Burn DJ, Chinnery PF, Sherman S, Vieregge P, Litvan I, Gillis T, MacDonald ME, Myers RH, Gusella JF. 2006. Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Arch Neurol 63:826-832.
133. Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H. 2004. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5: 213-218.
134. Tan EK, Khajavi M, Thornby JI, Nagamitsu S, Jankovic J, Ashizawa T. 2000. Variability and validity of polymorphism association studies in Parkinson's disease. Neurology 55:533-538.
135. Tan LC, Tanner CM, Chen R, Chan P, Farrer M, Hardy J, Langston JW. 2003a. Marked variation in clinical presentation and age of onset in a family with a heterozygous parkin mutation. Mov Disord 18:758-763.
136. Tan EK, Tan C, Fook-Chong SM, Lum SY, Chai A, Chung H, Shen H, Zhao Y, Teoh ML, Yih Y, Pavanni R, Chandran VR, Wong MC. 2003b. Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese. J Neurol Sci 216: 163-167.
137. Tan EK, Chai A, Teo YY, Zhao Y, Tan C, Shen H, Chandran VR, Teoh ML, Yih Y, Pavanni R, Wong MC, Puvan K, Lo YL, Yap E. 2004a. Alpha-synuclein haplotypes implicated in risk of Parkinson's disease. Neurology 62:128-131.
138. Tan EK, Tan C, Zhao Y, Yew K, Shen H, Chandran VR, Teoh ML, Yih Y, Pavanni R, Wong MC. 2004b. Genetic analysis of DJ-1 in a cohort Parkinson's disease patients of different ethnicity. Neurosci Lett 367: 109-112.
139. Tan EK, Puong KY, Chan DK, Yew K, Fook-Chong S, Shen H, Ng PW, Woo J, Yuen Y, Pavanni R, Wong MC, Puvan K, Zhao Y. 2005a. Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association. Hum Genet 118: 484-488.
140. Tan EK, Shen H, Tan JM, Lim KL, Fook-Chong S, Hu WP, Paterson MC, Chandran VR, Yew K, Tan C, Yuen Y, Pavanni R, Wong MC, Puvan K, Zhao Y. 2005b. Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease. Neurogenetics 6:179-184.
141. Tan EK, Yew K, Chua E, Shen H, Jamora RD, Lee E, Puong KY, Zhao Y, Pavanni R, Wong MC, Puvan K, Yih Y, Tan LC. 2005c. Analysis of PINK1 in Asian patients with familial parkinsonism. Clin Genet 68: 468-470.
142. Tan EK, Shen H, Tan LC, Farrer M, Yew K, Chua E, Jamora RD, Puvan K, Puong KY, Zhao Y, Pavanni R, Wong MC, Yih Y, Skipper L, Liu JJ. 2005d. The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease patients. Neurosci Lett 384:327-329.
143. Tan EK, Jankovic J. 2006a. Genetic testing in Parkinson disease: promises and pitfalls. Arch Neurol 63:1232-1237.
144. Tan EK, Puong KY, Fook-Chong S, Chua E, Shen H, Yuen Y, Pavanni R, Wong MC, Puvan K, Zhao Y. 2006b. Case-control study of UCHL1 S18Y variant in Parkinson's disease. Mov Disord 21:1765-1768.
145. Tan EK, Yew K, Chua E, Puvan K, Shen H, Lee E, Puong KY, Zhao Y, Pavanni R, Wong MC, Jamora D, de Silva D, Moe KT, Woon FP, Yuen Y, Tan L. 2006c. PINK1 mutations in sporadic early-onset Parkinson's disease. Mov Disord 21:789-793.
146. Tan EK, Skipper L, Chua E, Wong MC, Pavanni R, Bonnard C, Kolatkar P, Liu JJ. 2006d. Analysis of 14 LRRK2 mutations in Parkinson's plus syndromes and late-onset Parkinson's disease. Mov Disord 21:997-1001.
147. Tan EK, Skipper L, Tan LL, Liu JJ. 2007a. LRRK2 G2019S founder haplotype in Chinese. Mov Disord 22:105-107.
148. Tan EK, Zhao Y, Skipper L, Tan MG, Di Fonzo A, Sun L, Fook-Chong S, Tang S, Chua E, Yuen Y, Tan L, Pavanni R, Wong MC, Kolatkar P, Lu CS, Bonifati V, Liu JJ. 2007b. The LRRK2 Gly2385R variant is associated with risk of Parkinson's disease: clinical and genetic evidence. Hum Genet 120:857-863.
149. Tang B, Xiong H, Sun P, Zhang Y, Wang D, Hu Z, Zhu Z, Ma H, Pan Q, Xia JH, Xia K, Zhang Z. 2006. Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease. Hum Mol Genet 15:1816-1825.
150. Tanner CM, Ottman R, Goldman SM, Ellenberg J, Chan P, Mayeux R, Langston JW. 1999. Parkinson disease in twins: an etiologic study. JAMA 281:341-346.
151. Taylor JP, Mata IF, Farrer MJ. 2006. LRRK2: a common pathway for parkinsonism, pathogenesis and prevention? Trends Mol Med 12:76-82.
152. Tretter L, Sipos I, Adam-Vizi V. 2004. Initiation of neuronal damage by complex I deficiency and oxidative stress in Parkinson's disease. Neurochem Res 29:569-577.
153. Uversky VN. 2003. A protein-chameleon: conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders. J Biomol Struct Dyn 21:211-234.
154. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW. 2004a. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304:1158-1160.
155. Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, Bentivoglio AR. 2004b. PINK1 mutations are associated with sporadic early-onset parkinsonism. Ann Neurol 6: 336-341.
156. von Coelln R, Dawson VL, Dawson TM. 2004a. Parkin-associated Parkinson's disease. Cell Tissue Res 318:175-184.
157. von Coelln R, Thomas B, Savitt JM, Lim KL, Sasaki M, Hess EJ, Dawson VL, Dawson TM. 2004b. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc Natl Acad Sci USA 101:10744-10749.
158. Wang C, Tan JM, Ho MW, Zaiden N, Wong SH, Chew CL, Eng PW, Lim TM, Dawson TM, Lim KL. 2005. Alterations in the solubility and intracellular localization of parkin by several familial Parkinson's disease-linked point mutations. J Neurochem 93:422-431.
159. Waragai M, Wei J, Fujita M, Nakai M, Ho GJ, Masliah E, Akatsu H, Yamada T, Hashimoto M. 2006. Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson's disease. Biochem Biophys Res Commun 345:967-972.
160. West A, Periquet M, Lincoln S, Lucking CB, Nicholl D, Bonifati V, Rawal N, Gasser T, Lohmann E, Deleuze JF, Maraganore D, Levey A, Wood N, Durr A, Hardy J, Brice A, Farrer M. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility on Parkinson's Disease. 2002a. Complex relationship between Parkin mutations and Parkinson disease. Am J Med Genet 114: 584-591.
161. West AB, Maraganore D, Crook J, Lesnick T, Lockhart PJ, Wilkes KM, Kapatos G, Hardy JA, Farrer MJ. 2002b. Functional association of the parkin gene promoter with idiopathic Parkinson's disease. Hum Mol Genet 11:2787-2792.
162. West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM. 2005. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102:16842-16847.
163. Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J. 1989. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246:670-673.
164. Wu RM, Bounds R, Lincoln S, Hulihan M, Lin CH, Hwu WL, Chen J, Gwinn-Hardy K, Farrer M. 2005. Parkin mutations and early-onset parkinsonism in a Taiwanese cohort. Arch Neurol 62:82-87.
165. Xu J, Zhong N, Wang H, Elias JE, Kim CY, Woldman I, Pifl C, Gygi SP, Geula C, Yankner BA. 2005. The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum Mol Genet 14:1231-1241.
166. Yang F, Jiang Q, Zhao J, Ren Y, Sutton MD, Feng J. 2005a. Parkin stabilizes microtubules through strong binding mediated by three independent domains. J Biol Chem 280:17154-17162.
167. Yang Y, Gehrke S, Haque ME, Imai Y, Kosek J, Yang L, Beal MF, Nishimura I, Wakamatsu K, Ito S, Takahashi R, Lu B. 2005b. Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci USA 102:13670-13675.
168. Zabetian CP, Samii A, Mosley AD, Roberts JW, Leis BC, Yearout D, Raskind WH, Griffith A. 2005. A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. Neurology 65:741-744.
169. Zabetian CP, Hutter CM, Yearout D, Lopez AN, Factor SA, Griffith A, Leis BC, Bird TD, Nutt JG, Higgins DS, Roberts JW, Kay DM, Edwards KL, Samii A, Payami H. 2006a. LRRK2 G2019S in families with Parkinson disease who originated from Europe and the Middle East: evidence of two distinct founding events beginning two millennia ago. Am J Hum Genet 79:752-758.
170. Zabetian CP, Morino H, Ujike H, Yamamoto M, Oda M, Maruyama H, Izumi Y, Kaji R, Griffith A, Leis BC, Roberts JW, Yearout D, Samii A, Kawakami H. 2006b. Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease. Neurology 67:697-699.
171. Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG. 2004. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55:164-173.
172. Zhang L, Shimoji M, Thomas B, Moore DJ, Yu SW, Marupudi NI, Torp R, Torgner IA, Ottersen OP, Dawson TM, Dawson VL. 2005. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum Mol Genet 14:2063-2073.
173. Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL. 2006. The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. J Mol Biol 356:1036-1048.
174. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T. 2004. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601-607.