帕金森病中的突触、线粒体和溶酶体功能障碍。
Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson's Disease.
机构信息
Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
出版信息
Trends Neurosci. 2019 Feb;42(2):140-149. doi: 10.1016/j.tins.2018.11.001. Epub 2018 Nov 30.
Abstract
The discovery of genetic forms of Parkinson's disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endophilin A1), have also highlighted disruptions in synaptic vesicle endocytosis (SVE) as a significant contributor to disease pathogenesis. Additionally, the roles of other PD genes such as LRRK2, PRKN, and VPS35 in the regulation of SVE are beginning to emerge. Here we discuss the recent work on the contribution of dysfunctional SVE to midbrain dopaminergic neurons' selective vulnerability and highlight pathways that demonstrate the interplay of synaptic, mitochondrial, and lysosomal dysfunction in the pathogenesis of PD.
摘要
帕金森病（PD）遗传形式的发现强调了自噬/溶酶体和线粒体/氧化应激途径在疾病发病机制中的重要性。然而，最近发现的与 PD 相关的基因，包括 DNAJC6（辅助素）、SYNJ1（突触结合蛋白 1）和 PD 风险基因 SH3GL2（内收蛋白 A1），也强调了突触囊泡内吞作用（SVE）的破坏是导致疾病发病机制的一个重要因素。此外，LRRK2、PRKN 和 VPS35 等其他 PD 基因在 SVE 调节中的作用也开始显现。本文讨论了 SVE 功能障碍对中脑多巴胺能神经元选择性易损性的贡献，并强调了显示突触、线粒体和溶酶体功能障碍在 PD 发病机制中相互作用的途径。
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