研究与家族性帕金森病相关基因的协同作用。
Investigating convergent actions of genes linked to familial Parkinson's disease.
作者信息
Wolozin Benjamin, Saha Shamol, Guillily Maria, Ferree Andrew, Riley Misha
机构信息
Department of Pharmacology, Boston University School of Medicine, Boston, Mass. 02118-2526, USA.
出版信息
Neurodegener Dis. 2008;5(3-4):182-5. doi: 10.1159/000113697. Epub 2008 Mar 6.
Abstract
BACKGROUND
Mutations in LRRK2 are among the most frequent genetic changes identified in Parkinson's disease (PD), but how LRRK2 contributes to the pathophysiology of PD is not known.
OBJECTIVES
To investigate how expressing wild-type or G2019S LRRK2 modifies cellular responses to rotenone, a mitochondrial toxin.
METHODS
We investigated the vulnerability to mitochondrial toxins in Caenorhabditis elegans expressing wild-type or G2019S LRRK2.
RESULTS
We observed a powerful role for LRRK2 in mitochondrial biology. Overexpressing LRRK2 strongly protects C. elegans against rotenone toxicity. The G2019S LRRK2 construct also protected LRRK2 against rotenone, but to a lesser degree than wild-type LRRK2. Knockdown of lrk-1 potentiated rotenone toxicity.
CONCLUSIONS
These data suggest that LRRK1/2 regulate mitochondrial physiology.
摘要
背景
LRRK2 突变是帕金森病（PD）中最常见的基因变化之一，但 LRRK2 如何导致 PD 的病理生理过程尚不清楚。
目的
研究表达野生型或 G2019S 突变型 LRRK2 如何改变细胞对线粒体毒素鱼藤酮的反应。
方法
我们研究了表达野生型或 G2019S 突变型 LRRK2 的秀丽隐杆线虫对线粒体毒素的易感性。
结果
我们观察到 LRRK2 在线粒体生物学中发挥重要作用。过表达 LRRK2 能强烈保护秀丽隐杆线虫免受鱼藤酮毒性。G2019S 突变型 LRRK2 构建体也能保护线虫免受鱼藤酮毒性，但程度低于野生型 LRRK2。敲低 lrk-1 增强了鱼藤酮毒性。
结论
这些数据表明 LRRK1/2 调节线粒体生理学。
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