Genetic models of Parkinson disease

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1792, Issue 7, 2009, Pages 604-615

  Lim, Kah Leong ^a,b   Ng, Chee Hoe ^a  

^a NATIONAL NEUROSCIENCE INSTITUTE   (Singapore)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

DJ 1; Dopamine; LRRK2; MPTP; Neurodegeneration; Parkin; Parkinson disease; Pink1; Synuclein

Indexed keywords

ALPHA SYNUCLEIN; DJ 1 PROTEIN; DOPAMINE; GENE PRODUCT; LEUCINE RICH REPEAT KINASE 2; LEVODOPA; MUTANT PROTEIN; PARKIN; PROTEIN PINK1; UNCLASSIFIED DRUG;

ACCURACY; AUTOSOMAL DOMINANT DISORDER; AUTOSOMAL RECESSIVE DISORDER; CARBOXY TERMINAL SEQUENCE; CELL LOSS; DISEASE COURSE; DISEASE MODEL; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DOMINANT INHERITANCE; DOPAMINERGIC NERVE CELL; DOPAMINERGIC TRANSMISSION; FAMILIAL DISEASE; GENE IDENTIFICATION; GENE MUTATION; GENETIC DISORDER; GENETIC LINKAGE; HETEROZYGOTE; HUMAN; MAMMAL; MISSENSE MUTATION; MOTOR DYSFUNCTION; MUTATIONAL ANALYSIS; NERVE CELL LESION; NERVE DEGENERATION; NEUROPROTECTION; NIGRONEOSTRIATAL SYSTEM; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PARKINSONISM; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; SYMPTOM;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; MODELS, GENETIC; PARKINSON DISEASE;

ANIMALIA; MAMMALIA;

EID: 68649114338     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2008.10.005     Document Type: Review

References (157)

1. Jankovic J. Parkinson's disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79 (2008) 368-376
2. Braak H., Del Tredici K., Rub U., de Vos R.A., Jansen Steur E.N., and Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol. Aging 24 (2003) 197-211
3. Zarow C., Lyness S.A., Mortimer J.A., and Chui H.C. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch. Neurol. 60 (2003) 337-341
4. Lewy F.H. Paralysis agitans. I. Pathologische anatomie. Handbuch der neurologie (1912) 920-933
5. Tanaka M., Kim Y.M., Lee G., Junn E., Iwatsubo T., and Mouradian M.M. Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. J. Biol. Chem. 279 (2004) 4625-4631
6. Tompkins M.M., and Hill W.D. Contribution of somal Lewy bodies to neuronal death. Brain Res. 775 (1997) 24-29
7. Sulzer D. Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease. Trends Neurosci. 30 (2007) 244-250
8. Dawson T.M., and Dawson V.L. Molecular pathways of neurodegeneration in Parkinson's disease. Science 302 (2003) 819-822
9. Klein C., and Schlossmacher M.G. Parkinson disease, 10 years after its genetic revolution: multiple clues to a complex disorder. Neurology 69 (2007) 2093-2104
10. Thomas B., and Beal M.F. Parkinson's disease. Hum. Mol. Genet. 16 Spec No. 2 (2007) R183-R194
11. Bove J., Prou D., Perier C., and Przedborski S. Toxin-induced models of Parkinson's disease. NeuroRx 2 (2005) 484-494
12. 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., and 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. 102 (2005) 3413-3418
13. 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., and Nussbaum R.L. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276 (1997) 2045-2047
14. Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., and Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392 (1998) 605-608
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., and Heutink P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset Parkinsonism. Science 299 (2002) 256-259
16. 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., and Wood N.W. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 304 (2004) 1158-1160
17. 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., and Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44 (2004) 601-607
18. 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., and Singleton A.B. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44 (2004) 595-600
19. Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., Harta G., Brownstein M.J., Jonnalagada S., Chernova T., Dehejia A., Lavedan C., Gasser T., Steinbach P.J., Wilkinson K.D., and Polymeropoulos M.H. The ubiquitin pathway in Parkinson's disease. Nature 395 (1998) 451-452
20. Strauss K.M., Martins L.M., Plun-Favreau H., Marx F.P., Kautzmann S., Berg D., Gasser T., Wszolek Z., Muller T., Bornemann A., Wolburg H., Downward J., Riess O., Schulz J.B., and Kruger R. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum. Mol. Genet. 14 (2005) 2099-2111
21. Simon-Sanchez J., and Singleton A.B. Sequencing analysis of OMI/HTRA2 shows previously reported pathogenic mutations in neurologically normal controls. Hum. Mol. Genet. 17 (2008) 1988-1993
22. Ramirez A., Heimbach A., Grundemann J., Stiller B., Hampshire D., Cid L.P., Goebel I., Mubaidin A.F., Wriekat A.L., Roeper J., Al-Din A., Hillmer A.M., Karsak M., Liss B., Woods C.G., Behrens M.I., and Kubisch C. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat. Genet. 38 (2006) 1184-1191
23. Muqit M.M., and Feany M.B. Modelling neurodegenerative diseases in Drosophila: a fruitful approach?. Nat. Rev. Neurosci. 3 (2002) 237-243
24. Lakso M., Vartiainen S., Moilanen A.M., Sirvio J., Thomas J.H., Nass R., Blakely R.D., and Wong G. Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein. J. Neurochem. 86 (2003) 165-172
25. Murphy D.D., Rueter S.M., Trojanowski J.Q., and Lee V.M. Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J. Neurosci. 20 (2000) 3214-3220
26. Sharon R., Goldberg M.S., Bar-Josef I., Betensky R.A., Shen J., and Selkoe D.J. alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc. Natl. Acad. Sci. U. S. A. 98 (2001) 9110-9115
27. Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., Przuntek H., Epplen J.T., Schols L., and Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat. Genet. 18 (1998) 106-108
28. 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., and de Yebenes J.G. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55 (2004) 164-173
29. 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., and Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science 302 (2003) 841
30. Spillantini M.G., Schmidt M.L., Lee V.M., Trojanowski J.Q., Jakes R., and Goedert M. Alpha-synuclein in Lewy bodies. Nature 388 (1997) 839-840
31. Masliah E., Rockenstein E., Veinbergs I., Mallory M., Hashimoto M., Takeda A., Sagara Y., Sisk A., and Mucke L. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287 (2000) 1265-1269
32. Giasson B.I., Duda J.E., Quinn S.M., Zhang B., Trojanowski J.Q., and Lee V.M. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34 (2002) 521-533
33. Lee M.K., Stirling W., Xu Y., Xu X., Qui D., Mandir A.S., Dawson T.M., Copeland N.G., Jenkins N.A., and Price D.L. Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 8968-8973
34. van der Putten H., Wiederhold K.H., Probst A., Barbieri S., Mistl C., Danner S., Kauffmann S., Hofele K., Spooren W.P., Ruegg M.A., Lin S., Caroni P., Sommer B., Tolnay M., and Bilbe G. Neuropathology in mice expressing human alpha-synuclein. J. Neurosci. 20 (2000) 6021-6029
35. Gomez-Isla T., Irizarry M.C., Mariash A., Cheung B., Soto O., Schrump S., Sondel J., Kotilinek L., Day J., Schwarzschild M.A., Cha J.H., Newell K., Miller D.W., Ueda K., Young A.B., Hyman B.T., and Ashe K.H. Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice. Neurobiol. Aging 24 (2003) 245-258
36. Matsuoka Y., Vila M., Lincoln S., McCormack A., Picciano M., LaFrancois J., Yu X., Dickson D., Langston W.J., McGowan E., Farrer M., Hardy J., Duff K., Przedborski S., and Di Monte D.A. Lack of nigral pathology in transgenic mice expressing human alpha-synuclein driven by the tyrosine hydroxylase promoter. Neurobiol. Dis. 8 (2001) 535-539
37. Richfield E.K., Thiruchelvam M.J., Cory-Slechta D.A., Wuertzer C., Gainetdinov R.R., Caron M.G., Di Monte D.A., and Federoff H.J. Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp. Neurol. 175 (2002) 35-48
38. Thiruchelvam M.J., Powers J.M., Cory-Slechta D.A., and Richfield E.K. Risk factors for dopaminergic neuron loss in human alpha-synuclein transgenic mice. Eur. J. Neurosci. 19 (2004) 845-854
39. 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., and 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. 26 (2006) 3942-3950
40. Wakamatsu M., Ishii A., Iwata S., Sakagami J., Ukai Y., Ono M., Kanbe D., Muramatsu S., Kobayashi K., Iwatsubo T., and Yoshimoto M. Selective loss of nigral dopamine neurons induced by overexpression of truncated human alpha-synuclein in mice. Neurobiol. Aging 29 (2008) 574-585
41. Baba M., Nakajo S., Tu P.H., Tomita T., Nakaya K., Lee V.M., Trojanowski J.Q., and Iwatsubo T. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am. J. Pathol. 152 (1998) 879-884
42. Crowther R.A., Jakes R., Spillantini M.G., and Goedert M. Synthetic filaments assembled from C-terminally truncated alpha-synuclein. FEBS Lett. 436 (1998) 309-312
43. Murray I.V., Giasson B.I., Quinn S.M., Koppaka V., Axelsen P.H., Ischiropoulos H., Trojanowski J.Q., and Lee V.M. Role of alpha-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry 42 (2003) 8530-8540
44. Liu C.W., Giasson B.I., Lewis K.A., Lee V.M., Demartino G.N., and Thomas P.J. A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: implications for pathogenesis of Parkinson disease. J. Biol. Chem. 280 (2005) 22670-22678
45. Li W., West N., Colla E., Pletnikova O., Troncoso J.C., Marsh L., Dawson T.M., Jakala P., Hartmann T., Price D.L., and Lee M.K. Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 2162-2167
46. Nuber S., Petrasch-Parwez E., Winner B., Winkler J., von Horsten S., Schmidt T., Boy J., Kuhn M., Nguyen H.P., Teismann P., Schulz J.B., Neumann M., Pichler B.J., Reischl G., Holzmann C., Schmitt I., Bornemann A., Kuhn W., Zimmermann F., Servadio A., and Riess O. Neurodegeneration and motor dysfunction in a conditional model of Parkinson's disease. J. Neurosci. 28 (2008) 2471-2484
47. Kirik D., Rosenblad C., Burger C., Lundberg C., Johansen T.E., Muzyczka N., Mandel R.J., and Bjorklund A. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J. Neurosci. 22 (2002) 2780-2791
48. Lo Bianco C., Ridet J.L., Schneider B.L., Deglon N., and 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. 99 (2002) 10813-10818
49. St Martin J.L., Klucken J., Outeiro T.F., Nguyen P., Keller-McGandy C., Cantuti-Castelvetri I., Grammatopoulos T.N., Standaert D.G., Hyman B.T., and McLean P.J. Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. J. Neurochem. 100 (2007) 1449-1457
50. Ulusoy A., Bjorklund T., Hermening S., and Kirik D. In vivo gene delivery for development of mammalian models for Parkinson's disease. Exp. Neurol. 209 (2008) 89-100
51. Feany M.B., and Bender W.W. A Drosophila model of Parkinson's disease. Nature 404 (2000) 394-398
52. Auluck P.K., Chan H.Y., Trojanowski J.Q., Lee V.M., and Bonini N.M. Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295 (2002) 865-868
53. Klucken J., Shin Y., Masliah E., Hyman B.T., and McLean P.J. Hsp70 Reduces alpha-Synuclein Aggregation and Toxicity. J. Biol. Chem. 279 (2004) 25497-25502
54. Auluck P.K., and Bonini N.M. Pharmacological prevention of Parkinson disease in Drosophila. Nat. Med. 8 (2002) 1185-1186
55. Auluck P.K., Meulener M.C., and Bonini N.M. Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila. J. Biol. Chem. 280 (2005) 2873-2878
56. Chen L., and Feany M.B. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat. Neurosci. 8 (2005) 657-663
57. Fujiwara H., Hasegawa M., Dohmae N., Kawashima A., Masliah E., Goldberg M.S., Shen J., Takio K., and Iwatsubo T. alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 4 (2002) 160-164
58. Wakamatsu M., Ishii A., Ukai Y., Sakagami J., Iwata S., Ono M., Matsumoto K., Nakamura A., Tada N., Kobayashi K., Iwatsubo T., and Yoshimoto M. Accumulation of phosphorylated alpha-synuclein in dopaminergic neurons of transgenic mice that express human alpha-synuclein. J. Neurosci. Res. 85 (2007) 1819-1825
59. Yang Y., Nishimura I., Imai Y., Takahashi R., and Lu B. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Neuron 37 (2003) 911-924
60. Pesah Y., Burgess H., Middlebrooks B., Ronningen K., Prosser J., Tirunagaru V., Zysk J., and Mardon G. Whole-mount analysis reveals normal numbers of dopaminergic neurons following misexpression of alpha-Synuclein in Drosophila. Genesis 41 (2005) 154-159
61. D. Drobysheva, K. Ameel, B. Welch, E. Ellison, K. Chaichana, B. Hoang, S. Sharma, W. Neckameyer, I. Srinakevitch, K.J. Murphy and A. Schmid, An Optimized Method for Histological Detection of Dopaminergic Neurons in Drosophila melanogaster, J Histochem Cytochem (in press).
62. Kuwahara T., Koyama A., Gengyo-Ando K., Masuda M., Kowa H., Tsunoda M., Mitani S., and Iwatsubo T. Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. J. Biol. Chem. 281 (2006) 334-340
63. van Ham T.J., Thijssen K.L., Breitling R., Hofstra R.M., Plasterk R.H., and Nollen E.A. C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet. 4 (2008) e1000027
64. Kuwahara T., Koyama A., Koyama S., Yoshina S., Ren C.H., Kato T., Mitani S., and Iwatsubo T. A Systematic RNAi Screen Reveals Involvement of Endocytic Pathway in Neuronal Dysfunction in {alpha}-Synuclein Transgenic C. elegans. Hum. Mol. Genet. 17 (2008) 2994-3009
65. Imai Y., Soda M., and Takahashi R. Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 275 (2000) 35661-35664
66. Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S., Shimizu N., Iwai K., Chiba T., Tanaka K., and Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25 (2000) 302-305
67. Zhang Y., Gao J., Chung K.K., Huang H., Dawson V.L., and 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. 97 (2000) 13354-13359
68. Choi P., Snyder H., Petrucelli L., Theisler C., Chong M., Zhang Y., Lim K., Chung K.K., Kehoe K., D'Adamio L., Lee J.M., Cochran E., Bowser R., Dawson T.M., and Wolozin B. SEPT5_v2 is a parkin-binding protein. Brain Res. Mol. Brain Res. 117 (2003) 179-189
69. Staropoli J.F., McDermott C., Martinat C., Schulman B., Demireva E., and Abeliovich A. Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron 37 (2003) 735-749
70. Imai Y., Soda M., Inoue H., Hattori N., Mizuno Y., and Takahashi R. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105 (2001) 891-902
71. Corti O., Hampe C., Koutnikova H., Darios F., Jacquier S., Prigent A., Robinson J.C., Pradier L., Ruberg M., Mirande M., Hirsch E., Rooney T., Fournier A., and Brice A. The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration. Hum. Mol. Genet. 12 (2003) 1427-1437
72. Ko H.S., von Coelln R., Sriram S.R., Kim S.W., Chung K.K., Pletnikova O., Troncoso J., Johnson B., Saffary R., Goh E.L., Song H., Park B.J., Kim M.J., Kim S., Dawson V.L., and Dawson T.M. Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death. J. Neurosci. 25 (2005) 7968-7978
73. Ko H.S., Kim S.W., Sriram S.R., Dawson V.L., and Dawson T.M. Identification of far upstream element-binding protein-1 as an authentic Parkin substrate. J. Biol. Chem. 281 (2006) 16193-16196
74. Hayashi S., Wakabayashi K., Ishikawa A., Nagai H., Saito M., Maruyama M., Takahashi T., Ozawa T., Tsuji S., and Takahashi H. An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene. Mov. Disord. 15 (2000) 884-888
75. Mori H., Kondo T., Yokochi M., Matsumine H., Nakagawa-Hattori Y., Miyake T., Suda K., and Mizuno Y. Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology 51 (1998) 890-892
76. Takahashi H., Ohama E., Suzuki S., Horikawa Y., Ishikawa A., Morita T., Tsuji S., and Ikuta F. Familial juvenile parkinsonism: clinical and pathologic study in a family. Neurology 44 (1994) 437-441
77. 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., and Shen J. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J. Biol. Chem. 278 (2003) 43628-43635
78. 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., and Garcia de Yebenes J. Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum. Mol. Genet. 12 (2003) 2277-2291
79. Perez F.A., and Palmiter R.D. Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 2174-2179
80. Von Coelln R., Thomas B., Savitt J.M., Lim K.L., Sasaki M., Hess E.J., Dawson V.L., and Dawson T.M. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 10744-10749
81. Lockhart P.J., O'Farrell C.A., and Farrer M.J. It's a double knock-out! The quaking mouse is a spontaneous deletion of parkin and parkin co-regulated gene (PACRG). Mov. Disord. 19 (2004) 101-104
82. Lorenzetti D., Antalffy B., Vogel H., Noveroske J., Armstrong D., and Justice M. The neurological mutant quaking(viable) is Parkin deficient. Mamm. Genome 15 (2004) 210-217
83. Le Saux F., Besson M.J., and Maurin Y. Abnormal postnatal ontogeny of the locus coeruleus in the epileptic mutant mouse quaking. Brain Res. Dev. Brain Res. 136 (2002) 197-205
84. Palacino J.J., Sagi D., Goldberg M.S., Krauss S., Motz C., Wacker M., Klose J., and Shen J. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J. Biol. Chem. 279 (2004) 18614-18622
85. Casarejos M.J., Menendez J., Solano R.M., Rodriguez-Navarro J.A., Garcia de Yebenes J., and Mena M.A. Susceptibility to rotenone is increased in neurons from parkin null mice and is reduced by minocycline. J. Neurochem. 97 (2006) 934-946
86. Darios F., Corti O., Lucking C.B., Hampe C., Muriel M.P., Abbas N., Gu W.J., Hirsch E.C., Rooney T., Ruberg M., and Brice A. Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum. Mol. Genet. 12 (2003) 517-526
87. Kuroda Y., Mitsui T., Kunishige M., and Matsumoto T. Parkin affects mitochondrial function and apoptosis in neuronal and myogenic cells. Biochem. Biophys. Res. Commun. 348 (2006) 787-793
88. Kuroda Y., Mitsui T., Kunishige M., Shono M., Akaike M., Azuma H., and Matsumoto T. Parkin enhances mitochondrial biogenesis in proliferating cells. Hum. Mol. Genet. 15 (2006) 883-895
89. Wang C., Ko H.S., Thomas B., Tsang F., Chew K.C., Tay S.P., Ho M.W., Lim T.M., Soong T.W., Pletnikova O., Troncoso J., Dawson V.L., Dawson T.M., and Lim K.L. Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function. Hum. Mol. Genet. 14 (2005) 3885-3897
90. Lo Bianco C., Schneider B.L., Bauer M., Sajadi A., Brice A., Iwatsubo T., and Aebischer P. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 17510-17515
91. Yamada M., Mizuno Y., and Mochizuki H. Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson's disease. Hum. Gene Ther. 16 (2005) 262-270
92. Vercammen L., Van der Perren A., Vaudano E., Gijsbers R., Debyser Z., Van den Haute C., and Baekelandt V. Parkin protects against neurotoxicity in the 6-hydroxydopamine rat model for Parkinson's disease. Mol. Ther. 14 (2006) 716-723
93. Paterna J.C., Leng A., Weber E., Feldon J., and Bueler H. DJ-1 and Parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice. Mol. Ther. 15 (2007) 698-704
94. Perez F.A., Curtis W.R., and Palmiter R.D. Parkin-deficient mice are not more sensitive to 6-hydroxydopamine or methamphetamine neurotoxicity. BMC Neurosci. 6 (2005) 71
95. Greene J.C., Whitworth A.J., Kuo I., Andrews L.A., Feany M.B., and Pallanck L.J. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 4078-4083
96. Pesah Y., Pham T., Burgess H., Middlebrooks B., Verstreken P., Zhou Y., Harding M., Bellen H., and Mardon G. Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress. Development 131 (2004) 2183-2194
97. Cha G.H., Kim S., Park J., Lee E., Kim M., Lee S.B., Kim J.M., Chung J., and Cho K.S. Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 10345-10350
98. Whitworth A.J., Theodore D.A., Greene J.C., Benes H., Wes P.D., and 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. 102 (2005) 8024-8029
99. Ved R., Saha S., Westlund B., Perier C., Burnam L., Sluder A., Hoener M., Rodrigues C.M., Alfonso A., Steer C., Liu L., Przedborski S., and Wolozin B. Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans. J. Biol. Chem. 280 (2005) 42655-42668
100. Greene J.C., Whitworth A.J., Andrews L.A., Parker T.J., and Pallanck L.J. Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum. Mol. Genet. 14 (2005) 799-811
101. Clark L.N., Afridi S., Karlins E., Wang Y., Mejia-Santana H., Harris J., Louis E.D., Cote L.J., Andrews H., Fahn S., Waters C., Ford B., Frucht S., Ottman R., and Marder K. Case-control study of the parkin gene in early-onset Parkinson disease. Arch. Neurol. 63 (2006) 548-552
102. Hilker R., Klein C., Ghaemi M., Kis B., Strotmann T., Ozelius L.J., Lenz O., Vieregge P., Herholz K., Heiss W.D., and Pramstaller P.P. Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene. Ann. Neurol. 49 (2001) 367-376
103. Khan N.L., Scherfler C., Graham E., Bhatia K.P., Quinn N., Lees A.J., Brooks D.J., Wood N.W., and Piccini P. Dopaminergic dysfunction in unrelated, asymptomatic carriers of a single parkin mutation. Neurology 64 (2005) 134-136
104. Oliveira S.A., Scott W.K., Martin E.R., Nance M.A., Watts R.L., Hubble J.P., Koller W.C., Pahwa R., Stern M.B., Hiner B.C., Ondo W.G., Allen Jr. F.H., Scott B.L., Goetz C.G., Small G.W., Mastaglia F., Stajich J.M., Zhang F., Booze M.W., Winn M.P., Middleton L.T., Haines J.L., Pericak-Vance M.A., and Vance J.M. Parkin mutations and susceptibility alleles in late-onset Parkinson's disease. Ann. Neurol. 53 (2003) 624-629
105. Klein C., Lohmann-Hedrich K., Rogaeva E., Schlossmacher M.G., and Lang A.E. Deciphering the role of heterozygous mutations in genes associated with parkinsonism. Lancet Neurol. 6 (2007) 652-662
106. Wang C., Lu R., Ouyang X., Ho M.W., Chia W., Yu F., and Lim K.L. Drosophila Overexpressing Parkin R275W Mutant Exhibits Dopaminergic Neuron Degeneration and Mitochondrial Abnormalities. J. Neurosci. 27 (2007) 8563-8570
107. Sang T.K., Chang H.Y., Lawless G.M., Ratnaparkhi A., Mee L., Ackerson L.C., Maidment N.T., Krantz D.E., and 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. 27 (2007) 981-992
108. Wang C., Lu R., Ouyang X., Ho M.W., Chia W., Yu F., and Lim K.L. Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities. J. Neurosci. 27 (2007) 8563-8570
109. Henn I.H., Gostner J.M., Lackner P., Tatzelt J., and Winklhofer K.F. Pathogenic mutations inactivate parkin by distinct mechanisms. J. Neurochem. 92 (2005) 114-122
110. Wang C., Tan J.M., Ho M.W., Zaiden N., Wong S.H., Chew C.L., Eng P.W., Lim T.M., Dawson T.M., and Lim K.L. Alterations in the solubility and intracellular localization of parkin by several familial Parkinson's disease-linked point mutations. J. Neurochem. 93 (2005) 422-431
111. Ardley H.C., Scott G.B., Rose S.A., Tan N.G., Markham A.F., and Robinson P.A. Inhibition of proteasomal activity causes inclusion formation in neuronal and non-neuronal cells overexpressing Parkin. Mol. Biol. Cell 14 (2003) 4541-4556
112. Cookson M.R., Lockhart P.J., McLendon C., O'Farrell C., Schlossmacher M., and Farrer M.J. RING finger 1 mutations in Parkin produce altered localization of the protein. Hum. Mol. Genet. 12 (2003) 2957-2965
113. Gu W.J., Corti O., Araujo F., Hampe C., Jacquier S., Lucking C.B., Abbas N., Duyckaerts C., Rooney T., Pradier L., Ruberg M., and Brice A. The C289G and C418R missense mutations cause rapid sequestration of human Parkin into insoluble aggregates. Neurobiol. Dis. 14 (2003) 357-364
114. Springer W., Hoppe T., Schmidt E., and Baumeister R. A Caenorhabditis elegans Parkin mutant with altered solubility couples alpha-synuclein aggregation to proteotoxic stress. Hum. Mol. Genet. 14 (2005) 3407-3423
115. Clark I.E., Dodson M.W., Jiang C., Cao J.H., Huh J.R., Seol J.H., Yoo S.J., Hay B.A., and Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature 441 (2006) 1162-1166
116. Park J., Lee S.B., Lee S., Kim Y., Song S., Kim S., Bae E., Kim J., Shong M., Kim J.M., and Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature 441 (2006) 1157-1161
117. Yang Y., Gehrke S., Imai Y., Huang Z., Ouyang Y., Wang J.W., Yang L., Beal M.F., Vogel H., and Lu B. Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 10793-10798
118. Yang Y., Gehrke S., Haque M.E., Imai Y., Kosek J., Yang L., Beal M.F., Nishimura I., Wakamatsu K., Ito S., Takahashi R., and 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. 102 (2005) 13670-13675
119. Yang Y., Ouyang Y., Yang L., Beal M.F., McQuibban A., Vogel H., and Lu B. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 7070-7075
120. Poole A.C., Thomas R.E., Andrews L.A., McBride H.M., Whitworth A.J., and Pallanck L.J. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 1638-1643
121. Zhou C., Huang Y., Shao Y., May J., Prou D., Perier C., Dauer W., Schon E.A., and Przedborski S. The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 12022-12027
122. Moore D.J. Parkin: a multifaceted ubiquitin ligase. Biochem. Soc. Trans. 34 (2006) 749-753
123. Kitada T., Pisani A., Porter D.R., Yamaguchi H., Tscherter A., Martella G., Bonsi P., Zhang C., Pothos E.N., and Shen J. Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 11441-11446
124. Gautier C.A., Kitada T., and Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 11364-11369
125. Haque M.E., Thomas K.J., D'Souza C., Callaghan S., Kitada T., Slack R.S., Fraser P., Cookson M.R., Tandon A., and Park D.S. Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 1716-1721
126. 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., and Downward J. The mitochondrial protease HtrA2 is regulated by Parkinson's disease-associated kinase PINK1. Nat. Cell Biol. 9 (2007) 1243-1252
127. Bogaerts V., Nuytemans K., Reumers J., Pals P., Engelborghs S., Pickut B., Corsmit E., Peeters K., Schymkowitz J., De Deyn P.P., Cras P., Rousseau F., Theuns J., and Van Broeckhoven C. Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease. Hum. Mutat. 29 (2008) 832-840
128. Pridgeon J.W., Olzmann J.A., Chin L.S., and Li L. PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biol. 5 (2007) e172
129. Weihofen A., Ostaszewski B., Minami Y., and Selkoe D.J. Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1. Hum. Mol. Genet. 17 (2008) 602-616
130. Taira T., Saito Y., Niki T., Iguchi-Ariga S.M., Takahashi K., and Ariga H. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep. 5 (2004) 213-218
131. Canet-Aviles R.M., Wilson M.A., Miller D.W., Ahmad R., McLendon C., Bandyopadhyay S., Baptista M.J., Ringe D., Petsko G.A., and Cookson M.R. The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 9103-9108
132. 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., and Shen J. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45 (2005) 489-496
133. Yamaguchi H., and Shen J. Absence of dopaminergic neuronal degeneration and oxidative damage in aged DJ-1-deficient mice. Mol. Neurodegener. 2 (2007) 10
134. Chen L., Cagniard B., Mathews T., Jones S., Koh H.C., Ding Y., Carvey P.M., Ling Z., Kang U.J., and Zhuang X. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem. 280 (2005) 21418-21426
135. Chandran J.S., Lin X., Zapata A., Hoke A., Shimoji M., Moore S.O., Galloway M.P., Laird F.M., Wong P.C., Price D.L., Bailey K.R., Crawley J.N., Shippenberg T., and Cai H. Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function. Neurobiol. Dis. 29 (2008) 505-514
136. Manning-Bog A.B., Caudle W.M., Perez X.A., Reaney S.H., Paletzki R., Isla M.Z., Chou V.P., McCormack A.L., Miller G.W., Langston J.W., Gerfen C.R., and Dimonte D.A. Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter. Neurobiol. Dis. 27 (2007) 141-150
137. 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., and Dawson V.L. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 14807-14812
138. 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., and Dawson V.L. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum. Mol. Genet. 14 (2005) 2063-2073
139. Menzies F.M., Yenisetti S.C., and Min K.T. Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr. Biol. 15 (2005) 1578-1582
140. Meulener M., Whitworth A.J., Armstrong-Gold C.E., Rizzu P., Heutink P., Wes P.D., Pallanck L.J., and Bonini N.M. Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease. Curr. Biol. 15 (2005) 1572-1577
141. 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., and 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. 102 (2005) 5215-5220
142. Park J., Kim S.Y., Cha G.H., Lee S.B., Kim S., and Chung J. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene 361 (2005) 133-139
143. Lavara-Culebras E., and Paricio N. Drosophila DJ-1 mutants are sensitive to oxidative stress and show reduced lifespan and motor deficits. Gene 400 (2007) 158-165
144. Meulener M.C., Xu K., Thomson L., Ischiropoulos H., and Bonini N.M. Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 12517-12522
145. West A.B., Moore D.J., Biskup S., Bugayenko A., Smith W.W., Ross C.A., Dawson V.L., and Dawson T.M. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 16842-16847
146. Smith W.W., Pei Z., Jiang H., Dawson V.L., Dawson T.M., and Ross C.A. Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat. Neurosci. 9 (2006) 1231-1233
147. 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., and Cookson M.R. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis. 23 (2006) 329-341
148. Taylor J.P., Mata I.F., and Farrer M.J. LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?. Trends Mol. Med. 12 (2006) 76-82
149. Mata I.F., Wedemeyer W.J., Farrer M.J., Taylor J.P., and Gallo K.A. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci. 29 (2006) 286-293
150. Greggio E., Lewis P.A., van der Brug M.P., Ahmad R., Kaganovich A., Ding J., Beilina A., Baker A.K., and Cookson M.R. Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. J. Neurochem. 102 (2007) 93-102
151. 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., and Dawson T.M. Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and kinase activities to neuronal toxicity. Hum. Mol. Genet. 16 (2007) 223-232
152. Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L., Dawson T.M., and Ross C.A. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 18676-18681
153. 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., and Smith W.W. A Drosophila model for LRRK2-linked parkinsonism. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 2693-2698
154. Lee S.B., Kim W., Lee S., and Chung J. Loss of LRRK2/PARK8 induces degeneration of dopaminergic neurons in Drosophila. Biochem. Biophys. Res. Commun. 358 (2007) 534-539
155. Wang D., Tang B., Zhao G., Pan Q., Xia K., Bodmer R., and Zhang Z. Dispensable role of Drosophila ortholog of LRRK2 kinase activity in survival of dopaminergic neurons. Mol. Neurodegener. 3 (2008) 3
156. Sakaguchi-Nakashima A., Meir J.Y., Jin Y., Matsumoto K., and Hisamoto N. LRK-1, a C. elegans PARK8-related kinase, regulates axonal-dendritic polarity of SV proteins. Curr. Biol. 17 (2007) 592-598
157. 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., and Rosenthal A. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25 (2000) 239-252