The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease

被引：424

作者：

Cookson, Mark R. ^{[1
]}

机构：

[1] NIA, Neurogenet Lab, NIH, Bethesda, MD 20982 USA

来源：

NATURE REVIEWS NEUROSCIENCE | 2010年 / 11卷 / 12期

基金：

美国国家卫生研究院;

关键词：

AUTOSOMAL-DOMINANT PARKINSONISM; ALPHA-SYNUCLEIN; LEUCINE-RICH-REPEAT-KINASE-2; LRRK2; CYTOPLASMIC LOCALIZATION; 14-3-3; BINDING; ROC DOMAIN; MUTATIONS; PROTEIN; PHOSPHORYLATION; GENE;

D O I：

10.1038/nrn2935

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Parkinson's disease, like many common age-related conditions, is now recognized to have a substantial genetic component. Here, I discuss how mutations in a large complex gene-leucine-rich repeat kinase 2 (LRRK2) - affect protein function, and I review recent evidence that LRRK2 mutations affect pathways that involve other proteins that have been implicated in Parkinson's disease, specifically a-synuclein and tau. These concepts can be used to understand disease processes and to develop therapeutic opportunities for the treatment of Parkinson's disease.

引用

页码：791 / 797

页数：7

共 74 条

[1] α-Synuclein: Membrane Interactions and Toxicity in Parkinson's Disease
Auluck, Pavan K.
Caraveo, Gabriela
Lindquist, Susan
[J]. ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26, 2010, 26 : 211 - 233
[2] Membrane Localization of LRRK2 Is Associated with Increased Formation of the Highly Active LRRK2 Dimer and Changes in Its Phosphorylation
Berger, Zdenek
Smith, Kelsey A.
LaVoie, Matthew J.
[J]. BIOCHEMISTRY, 2010, 49 (26) : 5511 - 5523
[3] Localization of LRRK2 to membranous and vesicular structures in mammalian brain
Biskup, Saskia
Moore, Darren J.
Celsi, Fulvio
Higashi, Shinji
West, Andrew B.
Andrabi, Shaida A.
Kurkinen, Kaisa
Yu, Seong-Woon
Savitt, Joseph M.
Waldvogel, Henry J.
Faull, Richard L. M.
Emson, Piers C.
Torp, Reldun
Ottersen, Ole P.
Dawson, Ted M.
Dawson, Valina L.
[J]. ANNALS OF NEUROLOGY, 2006, 60 (05) : 557 - 569
[4] Staging of brain pathology related to sporadic Parkinson's disease
Braak, H
Del Tredici, K
Rüb, U
de Vos, RAI
Steur, ENHJ
Braak, E
[J]. NEUROBIOLOGY OF AGING, 2003, 24 (02) : 197 - 211
[5] α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro
Burre, Jacqueline
Sharma, Manu
Tsetsenis, Theodoros
Buchman, Vladimir
Etherton, Mark R.
Suedhof, Thomas C.
[J]. SCIENCE, 2010, 329 (5999) : 1663 - 1667
[6] Microtubule assembly, organization and dynamics in axons and dendrites
Conde, Cecilia
Caceres, Alfredo
[J]. NATURE REVIEWS NEUROSCIENCE, 2009, 10 (05) : 319 - 332
[7] α-Synuclein and neuronal cell death
Cookson, Mark R.
[J]. MOLECULAR NEURODEGENERATION, 2009, 4
[8] Cookson MR, 2008, INT J CLIN EXP PATHO, V1, P217
[9] Di Fonzo A, 2005, LANCET, V365, P412
[10] DING X, 2009, PLOS ONE, V4, pNI187

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