Cellular effects of LRRK2 mutations
Cellular effects of LRRK2 mutations
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DOI：
10.1042/bst20120165
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发表时间：
2012-10-01
影响因子：
3.9
通讯作者：
Cookson, Mark R.
中科院分区：
文献类型：
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作者：
Cookson, Mark R.
LRRK2中的突变（富含亮氨酸的重复激酶2）是遗传性PD（帕金森氏病）的相对常见原因，但是突变导致疾病的机制知之甚少。在本文中，我讨论了细胞模型中有关LRRK2的了解，专门针对已用于嘲笑LRRK2突变对细胞表型的影响的测定。已经提出LRRK2表达会导致神经元活力的丧失，尽管因为它对这些细胞的神经突长度也有很强的影响，无论是否真正的毒性尚不清楚。同样，LRRK2突变体可以促进LRRK2从弥漫性胞质染色到更离散的结构的重新分布，至少在转染实验中达到的高表达水平下。这些表型与PD的相关性尚不清楚，需要大量的工作才能深入了解它们。
Mutations in LRRK2 (leucine-rich repeat kinase 2) are a relatively common cause of inherited PD (Parkinson's disease), but the mechanism(s) by which mutations lead to disease are poorly understood. In the present paper, I discuss what is known about LRRK2 in cellular models, focusing specifically on assays that have been used to tease apart the effects of LRRK2 mutations on cellular phenotypes. LRRK2 expression has been suggested to cause loss of neuronal viability, although because it also has a strong effect on the length of neurites on these cells, whether this is true toxicity or not is unclear. Also, LRRK2 mutants can promote the redistribution of LRRK2 from diffuse cytosolic staining to more discrete structures, at least at high expression levels achieved in transfection experiments. The relevance of these phenotypes for PD is not yet clear, and a great deal of work is needed to understand them in more depth.