Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson's disease.
Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson's disease.
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DOI：
10.1016/j.tips.2012.04.001
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发表时间：
2012-07
影响因子：
13.8
通讯作者：
Dawson TM
中科院分区：
文献类型：
--
作者：
Lee BD;Dawson VL;Dawson TM
帕金森病(PD)是由黑质多巴胺能神经元进行性变性引起的。尽管大多数帕金森病的病因仍不清楚，但在家族性帕金森病病例中识别特定的遗传缺陷以及这些基因所控制的信号通路已经为帕金森病的发病机制提供了巨大的洞察力。富亮氨酸重复蛋白激酶2(LRRK2)基因突变常见于家族性和散发性帕金森病。尽管目前对LRRK2激活的调控机制的了解有限，但越来越明显的是，LRRK2的病理突变的激酶活性异常与神经退行性变有关，这表明LRRK2的激酶活性是一个潜在的治疗靶点。此外，LRRK2抑制剂可能为了解LRRK2的病理生理作用以及帕金森病的病因提供有价值的工具。我们在这里讨论了靶向LRRK2作为帕金森病治疗策略的潜力和可行性。
Parkinson’s disease (PD) is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra. Although the etiology for most PD remains elusive, the identification of specific genetic defects in familial cases of PD and the signaling pathways governed by these genes has provided tremendous insight into PD pathogenesis. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequently found in familial and sporadic PD. Although current knowledge regarding the regulatory mechanisms of LRRK2 activation is limited, it is becoming increasingly evident that aberrant kinase activity of the pathologic mutants of LRRK2 is associated with neurodegeneration, suggesting that the kinase activity of LRRK2 is a potential therapeutic target. In addition, LRRK2 inhibitors might provide valuable tools to understand the pathophysiological and physiological roles of LRRK2 as well as the etiology of PD. We discuss here the potential and feasibility of targeting LRRK2 as a therapeutic strategy for PD.
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