导致神经退行性变的LRRK2信号通路。
LRRK2 Pathways Leading to Neurodegeneration.
作者信息
Cookson Mark R
机构信息
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, 35 Convent Drive, Bethesda, MD, 20892-3707, USA,
出版信息
Curr Neurol Neurosci Rep. 2015 Jul;15(7):42. doi: 10.1007/s11910-015-0564-y.
Mutations in LRRK2 are associated with inherited Parkinson's disease (PD) in a large number of families, and the genetic locus containing the LRRK2 gene contains a risk factor for sporadic PD. The LRRK2 protein contains several domains that suggest a role in cellular signaling, including a kinase domain. It is also clear that LRRK2 interacts, either physically or genetically, with several other important proteins implicated in PD, suggesting that LRRK2 may be a central player in the pathways that underlie parkinsonism. As such, LRRK2 has been proposed to be a plausible target for therapeutic intervention, with kinase inhibition being pursued most actively. However, there are still several fundamental aspects of LRRK2 biology and function that remain unresolved at this time. This review will focus on the key questions of normal function of LRRK2 and how this might be related to the pathophysiology of PD.
LRRK2基因的突变在大量家族性帕金森病（PD）中与遗传相关，且包含LRRK2基因的遗传位点是散发性PD的一个风险因素。LRRK2蛋白包含几个表明其在细胞信号传导中起作用的结构域，其中包括一个激酶结构域。同样明确的是，LRRK2在物理或遗传层面上与其他几个与PD相关的重要蛋白质相互作用，这表明LRRK2可能是帕金森综合征潜在通路中的核心参与者。因此，LRRK2已被认为是一个合理的治疗干预靶点，其中激酶抑制是最积极探索的方向。然而，目前LRRK2生物学和功能的几个基本方面仍未得到解决。本综述将聚焦于LRRK2正常功能的关键问题，以及这可能如何与PD的病理生理学相关。
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