分子侣伴蛋白介导的自噬障碍在神经退行性病变中的作用  

The role of chaperone-mediated autophagy in neurodegenerative diseases

作　　者：张学凯[1,2] 时晶[1] 田金洲[1] 

机构地区：[1]北京中医药大学东直门医院脑病科,北京100700 [2]神经退行性疾病和认知障碍研究组,曼彻斯特大学,皇家索尔褊德医院,曼彻斯特M68HD,英国

出　　处：《转化医学研究（电子版）》2013年第1期37-53,共17页Translational Medicine Research(Electronic Edition)

基　　金：国家重大新药创制专项(2011ZX09302-006);国家“十一五”科技支撑项目(2009BA177B09);高等学校学科创新引智基地计划(B08006);慢性病的中医药二级预防研究(No:Z111107056811043);北京中医药大学神经变性病创新团队(2011-CXTD-21)等资助~~

摘　　要：分子偶伴介导的白噬（chaperone—mediatedautophagy，CMA）是单个可溶性蛋白在溶酶体进行选择性降解的一种白噬途径，其特点是所要进行降解的蛋白直接穿过溶酶体膜到达溶酶体内腔进行降解，与其他自噬途径通过睫泡介导的特点完全不同。选择性降解、底物直接转位这两大特点决定丫CMA所参与的各种生理功能以及CMA障碍所引起的不同疾病。最近的研究表明，随着年龄下降的CMA功能是多种疾病的加重因素。本文将简要综述CMA功能相关的分子机制以及通过这一途径进行的溶酶体的选择性降解相关生理的最新研究，也将评述CMA障碍的细胞结局和CMA障碍与神经退行性病变的关系。Cliaperonemediated autophagy （CMA） is a selective lysosomal autophagy pathway for the degradation of in dividual cytosolic soluble proteins. It is different from other autophagic pathways due to its selectivity and distinctive mechanism by which substrates reach the lysosomal lumen. These characteristics of selective targeting and direct substrates translocation de termine the contribution of CMA to different physiological functions and the type of pathological conditions associated with CMA dysfunction. Alterations in CMA have recently been shown to underlie some severe human disorders for which the de cline with age in the activity of this pathway might become a major aggravating factor. In this review, we willbriefly summa rize recent findings＂ o11 the molecular mechanisms behind CMA function, and describe the physiological relevance of the selec tive lysosomal degradation through this pathway. We also comment on the cellular consequences of CMA malfunction and the well established relationship between CMA dysfunction and neurodegenerative diseases.

关 键 词：分子侣伴介导的自噬(CMA) 神经退行性病变 

分 类 号：R741[医药卫生—神经病学与精神病学]