Leucine-rich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson's disease.
Leucine-rich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson's disease.
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DOI：
10.1002/jnr.21949
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发表时间：
2009-05-01
影响因子：
4.2
通讯作者：
Wilson-Delfosse, Amy L.
中科院分区：
文献类型：
--
作者：
Gandhi, Payal N.;Chen, Shu G.;Wilson-Delfosse, Amy L.
帕金森病（PD）是最常见的神经退行性运动障碍，65岁以后的患病率超过1%。编码富含亮氨酸重复序列激酶2（LRRK2）的基因突变最近被认为与常染色体显性遗传的迟发型PD有关，临床上无法与典型的特发性疾病区分。LRRK2是一种多结构域蛋白，含有几个蛋白质相互作用基序以及GT3和蛋白激酶活性的双酶结构域。疾病相关突变在蛋白质的多结构域结构中发现。然而，LRRK2在PD致病基因中是独特的，因为错义突变G2019S不仅是家族性PD的常见决定因素，而且也是散发性PD的常见决定因素。因此，LRRK2已经成为对抗PD的有希望的治疗靶标。本文综述了LRRK2的结构域结构，氨基酸取代和潜在的功能作用的知识现状。
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder with a prevalence of more than 1% after the age of 65 years. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have recently been linked to autosomal dominant, late-onset PD that is clinically indistinguishable from typical, idiopathic disease. LRRK2 is a multi-domain protein containing several protein interaction motifs as well as dual enzymatic domains of GTPase and protein kinase activities. Disease-associated mutations are found throughout the multi-domain structure of the protein. LRRK2, however, is unique among the PD-causing genes because a missense mutation, G2019S, is a frequent determinant of not only familial, but also of sporadic PD. Thus, LRRK2 has emerged as a promising therapeutic target for combating PD. This article reviews the current state of knowledge regarding the domain structure, amino acid substitutions, and potential functional roles of LRRK2.
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