[an error occurred while processing this directive]
en

Function study advances of Parkinson¢s disease related genes

Expand
  • China Academy of Chinese Medical Science, the Experimental Research Center, Beijing 100700, China

Received date: 2009-11-24

  Revised date: 2010-03-19

  Online published: 2010-08-23

Abstract

Parkinson¢s disease (PD) is a common extrapyramidal disease, of which the cardinal symptoms are hypokinesia, muscular rigidity, and tremor. The main pathological characteristics of this disease are loss of dopamine neurons in substantia nigra pars compacta, and residual neurons often contain Lewy bodies. The PD pathogenesis is still not well known, while it is generally recognized that age and environmental factors participate in it. In recent years, genetic research on PD has made considerable progresses that genetic factors play important roles on the pathogenesis of PD, and multiple PD related genes, such as SNCA, LRRK2, PINK1, parkin, UCHL1, and DJ1, have been identified. This article summarizes recent progresses on these genes to provide reference for PD study.

Cite this article

WANG Xiang-Meng, WANG Dan-Qiao, HONG Xiao-Yan . Function study advances of Parkinson¢s disease related genes[J]. Hereditas(Beijing), 2010 , 32(8) : 779 -784 . DOI: 10.3724/SP.J.1005.2010.00779

References

[1] Lang AE, Lozano AM. Parkinson’s disease. First of two parts. N Engl J Med, 1998, 339(15): 1044–1053. [2] Papapetropoulos S, Adi N, Ellul J, Argyriou AA, Chroni E. A prospective study of familial versus sporadic Parkin- son's disease. Neurodegener Dis, 2007, 4(6): 424–427. [3] Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson's disease. Annu Rev Neurosci, 2005, 28: 57–87. [4] Farrer MJ. Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet, 2006, 7(4): 306–318. [5] van der Putten H, Wiederhold KH, Probst A, Barbieri S, Mistl C, Danner S, Kauffmann S, Hofele K, Spooren WP, Ruegg MA, Lin S, Caroni P, Sommer B, Tolnay M, Bilbe G. Neuropathology in mice expressing human alpha-synu clein. J Neurosci, 2000, 20(16): 6021–6029. [6] Feany MB, Bender WW. A Drosophila model of Parkin- son's disease. Nature, 2000, 404(6776): 394–398. [7] Kuwahara T, Koyama A, Gengyo-Ando K, Masuda M, Kowa H, Tsunoda M, Mitani S, Iwatsubo T. Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. J Biol Chem, 2006, 281 (1): 334–340. [8] Vartiainen S, Pehkonen P, Lakso M, Nass R, Wong G. Identification of gene expression changes in transgenic C. elegans overexpressing human alpha-synuclein. Neurobiol Dis, 2006, 22(3): 477–486. [9] Kuwahara T, Koyama A, Koyama S, Yoshina S, Ren CH, Kato T, Mitani S, Iwatsubo T. A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in alpha-synuclein transgenic C. elegans. Hum Mol Genet, 2008, 17(19): 2997–3009. [10] MacLeod D, Dowman J, Hammond R, Leete T, Inoue K, Abeliovich A. The familial Parkinsonism gene LRRK2 regulates neurite process morphology. Neuron, 2006, 52(4): 587–593. [11] Shin N, Jeong H, Kwon J, Heo HY, Kwon JJ, Yun HJ, Kim CH, Han BS, Tong Y, Shen J, Hatano T, Hattori N, Kim KS, Chang S, Seol W. LRRK2 regulates synaptic vesicle endocytosis. Exp Cell Res, 2008, 314(10): 2055–2065. [12] Gloeckner CJ, Schumacher A, Boldt K, Ueffing M. The Parkinson disease-associated protein kinase LRRK2 ex- hibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro. J Neurochem, 2009, 109(4): 959–968. [13] Milosevic J, Schwarz SC, Ogunlade V, Meyer AK, Storch A, Schwarz J. Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation. Mol Neurodegener, 2009, 4: 25. [14] Gillardon F. Leucine-rich repeat kinase 2 phosphorylates brain tubulin-beta isoforms and modulates microtubule stability-a point of convergence in Parkinsonian neurode- generation? J Neurochem, 2009, 110(5): 1514–1522. [15] Alegre-Abarrategui J, Christian H, Lufino M, Mutihac R, Lourenco Venda L, Ansorge O, Wade-Martins R. LRRK2 regulates autophagic activity and localises to specific mem- brane microdomains in a novel human genomic reporter cel lular model. Hum Mol Genet, 2009, 18(21): 4022–4034. [16] Qing H, Wong W, McGeer EG, McGeer PL. Lrrk2 phos- phorylates alpha synuclein at serine 129: Parkinson dis- ease implications. Biochem Biophys Res Commun, 2009, 387(1): 149–152. [17] Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, Zhou C, Geghman K, Bogdanov M, Przedborski S, Beal MF, Burke RE, Li C. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkin- son's disease. Nat Neurosci, 2009, 12(7): 826–828. [18] Liu Z, Wang X, Yu Y, Li X, Wang T, Jiang H, Ren Q, Jiao Y, Sawa A, Moran T, Ross CA, Montell C, Smith WW. A Drosophila model for LRRK2-linked Parkinsonism. Proc Natl Acad Sci USA, 2008, 105(7): 2693–2698. [19] Petit A, Kawarai T, Paitel E, Sanjo N, Maj M, Scheid M, Chen F, Gu Y, Hasegawa H, Salehi-Rad S, Wang L, Ro- gaeva
Outlines

/