线粒体自噬参与帕金森病发病机制的研究进展  

Involvement of mitophagy in pathogenesis of Parkinson disease

作　　者：王英[1] 张强 乐卫东[1] 

机构地区：[1]大连医科大学附属第一医院辽宁省神经疾病转化医学中心,116021 [2]大连船舶康复医院康复科,辽宁省116011

出　　处：《中华临床医师杂志（电子版）》2015年第21期98-104,共7页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金重点项目(81430021);国家自然科学基金面上项目(81370470)

摘　　要：帕金森病是中老年人常见的中枢神经系统退行性疾病,近年的研究表明线粒体自噬是帕金森病的发病机制之一。目前已知帕金森病相关基因PINK1、PARKIN、SNCA、DJ-1、LRRK2以及ATP13A2和GBA均参与线粒体自噬的调节。其中PINK1参与线粒体代谢、线粒体动力和异常蛋白的降解过程,并参与PARKIN移位至受损线粒体触发线粒体自噬;PARKIN参与泛素-蛋白降解途径,调节自噬小体吞噬、降解陈旧线粒体,以保护线粒体DNA、维持线粒体呼吸链活性来发挥细胞保护作用;DJ-1参与细胞应激环境下线粒体活性和形态的调节;SNCA编码的α-突触核蛋白通过影响自噬小体的形成、调节线粒体动力和保持线粒体的钙平衡来调控线粒体自噬;LRRK2基因突变也可以引发线粒体自噬。此外,环境因素也可能直接或间接地对线粒体自噬产生调控。本文将对线粒体自噬与帕金森病之间的关联作一简要综述。Parkinson's disease is one of the most common neurodegenerative diseases in the elder populations. Recent studies have suggested that the mitophagy is one of the pathogenesis of Parkinson's disease. Parkinson's disease-related genes such asPINK1, PARKIN, SNCA, DJ-1, LRRK2, ATP13A2 and GBA are involved in the regulation of mitophagy. PINK1 modulates mitochondrial metabolism, mitochondrial dynamics and degradation of abnormal proteins, and participates in the mitochondrial PARKIN translocation and triggers mitophagy. PARKIN is involved in ubiquitin-protein degradation pathway, regulates autophagosomes swallow and degradation of damaged mitochondria to protect mitochondrial DNA, mitochondrial respiratory chain activity to maintain a protective effect against oxidative stress in cells. DJ-1 is also involved in the regulation of mitochondrial activity and cell morphology under stress conditions. SNCA encoding α-synuclein affects autophagy by the formation of autophagosome, regulates mitochondrial dynamics and maintains calcium balance to regulate mitophagy. LRRK2 mutation can also lead to mitophagy. Besides the genetic factors, environmental factors may also regulate mitophagy. This review discussed the association between Parkinson's disease and mitophagy.

关 键 词：Α突触核蛋白 线粒体 线粒体自噬 帕金森病 帕金森病相关基因 

分 类 号：R742.5[医药卫生—神经病学与精神病学]