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

被引：431
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
收藏
页码：791 / 797
页数：7
相关论文
共 74 条
[1]   α-Synuclein: Membrane Interactions and Toxicity in Parkinson's Disease [J].
Auluck, Pavan K. ;
Caraveo, Gabriela ;
Lindquist, Susan .
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 [J].
Berger, Zdenek ;
Smith, Kelsey A. ;
LaVoie, Matthew J. .
BIOCHEMISTRY, 2010, 49 (26) :5511-5523
[3]   Localization of LRRK2 to membranous and vesicular structures in mammalian brain [J].
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. .
ANNALS OF NEUROLOGY, 2006, 60 (05) :557-569
[4]   Staging of brain pathology related to sporadic Parkinson's disease [J].
Braak, H ;
Del Tredici, K ;
Rüb, U ;
de Vos, RAI ;
Steur, ENHJ ;
Braak, E .
NEUROBIOLOGY OF AGING, 2003, 24 (02) :197-211
[5]   α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro [J].
Burre, Jacqueline ;
Sharma, Manu ;
Tsetsenis, Theodoros ;
Buchman, Vladimir ;
Etherton, Mark R. ;
Suedhof, Thomas C. .
SCIENCE, 2010, 329 (5999) :1663-1667
[6]   Microtubule assembly, organization and dynamics in axons and dendrites [J].
Conde, Cecilia ;
Caceres, Alfredo .
NATURE REVIEWS NEUROSCIENCE, 2009, 10 (05) :319-332
[7]   α-Synuclein and neuronal cell death [J].
Cookson, Mark R. .
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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