Kinase activity of mutant LRRK2 mediates neuronal toxicity

被引：507

作者：

Smith, Wanli W.

Pei, Zhong

Jiang, Haibing

Dawson, Valina L.

Dawson, Ted M.

Ross, Christopher A.

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA

[4] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21287 USA

[5] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21287 USA

[6] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21287 USA

来源：

NATURE NEUROSCIENCE | 2006年 / 9卷 / 10期

关键词：

D O I：

10.1038/nn1776

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Mutations in the the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal- dominant Parkinson disease and some cases of sporadic Parkinson disease. Here we found that LRRK2 kinase activity was regulated by GTP via the intrinsic GTPase Roc domain, and alterations of LRRK2 protein that reduced kinase activity of mutant LRRK2 correspondingly reduced neuronal toxicity. These data elucidate the pathogenesis of LRRK2-linked Parkinson disease, potentially illuminate mechanisms of sporadic Parkinson disease and suggest therapeutic targets.

引用

页码：1231 / 1233

页数：3

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