Rab GTPases 在帕金森病发病机制中的新兴作用。

The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease.

机构信息

Bruce Lefroy Centre for Genetic Health Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.

出版信息

Mov Disord. 2018 Feb;33(2):196-207. doi: 10.1002/mds.27270. Epub 2018 Jan 9.

DOI:10.1002/mds.27270

PMID:29315801

Abstract

The identification of pathogenic mutations in Ras analog in brain 39B (RAB39B) and Ras analog in brain 32 (RAB32) that cause Parkinson's disease (PD) has highlighted the emerging role of protein trafficking in disease pathogenesis. Ras analog in brain (Rab) Guanosine triphosphatase (GTPase) function as master regulators of membrane trafficking, including vesicle formation, movement along cytoskeletal networks, and membrane fusion. Recent studies have linked Rab GTPases with α-synuclein, Leucine-rich repeat kinase 2, and Vacuolar protein sorting 35, 3 key proteins in PD pathogenesis. In this review, we discuss the various RAB GTPases associated with PD, current progress in the research, and potential future directions. Investigations into the function of RAB GTPases will likely provide significant insight into the etiology of PD and identify novel therapeutic targets for a currently incurable disease. © 2018 International Parkinson and Movement Disorder Society.

摘要

在 Ras 模拟物 in brain 39B（RAB39B）和 Ras 模拟物 in brain 32（RAB32）中鉴定出导致帕金森病（PD）的致病突变，突显了蛋白质运输在疾病发病机制中的新作用。Ras 模拟物 in brain（Rab）Guanosine 三磷酸酶（GTPase）作为膜运输的主要调节剂，包括囊泡形成、沿细胞骨架网络运动和膜融合。最近的研究将 Rab GTPases 与 α-突触核蛋白、富含亮氨酸重复激酶 2 和液泡蛋白分选 35 联系起来，这是 PD 发病机制中的 3 个关键蛋白。在这篇综述中，我们讨论了与 PD 相关的各种 RAB GTPases、目前的研究进展和潜在的未来方向。对 Rab GTPases 功能的研究可能会深入了解 PD 的病因，并为目前无法治愈的疾病确定新的治疗靶点。