囊泡转运在肌萎缩侧索硬化中的作用研究进展  

Research progress on vesicular trafficking in amyotrophic lateral sclerosis

作　　者：杨朝森 张晓明[1] YANG Chaosen;ZHANG Xiaoming(Department of Human Anatomy and Embryology,School of Basic Medical Sciences,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]浙江大学基础医学院解剖与组织胚胎学系,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2022年第3期380-387,共8页Journal of Zhejiang University(Medical Sciences)

摘　　要：囊泡转运是细胞利用囊泡完成细胞与环境间或细胞内各细胞器之间物质运输的基本生理过程。近年来,越来越多证据表明囊泡转运障碍在神经退行性疾病发病中起到关键作用。错误折叠蛋白质在异常囊泡转运的介导下,通过内吞作用、内体-溶酶体途径运输、内体逃逸和外泌体释放等方式,实现其在细胞间的传播,进一步加速疾病进展。肌萎缩侧索硬化(ALS)是一种以上下运动神经元的选择性死亡为特征的神经退行性疾病,其多种致病基因均与囊泡转运密切相关,如C9ORF72、TARDBP、SOD1等,能导致囊泡转运功能障碍。因此,通过调控囊泡转运相关蛋白,能阻止错误折叠蛋白质的沉积和传播,从而起到延缓ALS疾病发展的作用。本文通过综述文献,阐述了囊泡转运在ALS中的重要分子机制,以期为理解ALS致病机制和寻找潜在治疗手段提供新的视角。Vesicular trafficking is a basic physiological process by which vesicles transport materials between cells and environment(intercellular transport)and between different cellular compartments(intracellular trafficking).In recent years,more and more evidences have suggested that vesicular trafficking dysfunction plays a key role in pathogenesis of neurodegenerative diseases.Abnormal vesicular trafficking promotes the propagation of misfolded proteins by mechanisms involving endocytosis,endosomallysosomal pathway,endosomal escape and exosome release,leading to further acceleration of disease progression.Amyotrophic lateral sclerosis(ALS),as a neurodegenerative disease,is characterized by the selective death of upper and lower motor neurons.A variety of causative genes for ALS have been implicated in vesicle trafficking dysfunction,such as C9ORF72,TARDBP and SOD1.Therefore,the aggregation and propagation of misfolded proteins may be prevented through regulation of vesicle trafficking-related proteins,thus delay the progression of ALS.A more in-depth understanding of vesicular trafficking in ALS will be helpful in revealing the mechanism and clinical treatment of ALS.This review focuses on molecular mechanisms of vesicular trafficking in ALS,to provide reference for exploring new therapeutic strategies.

关 键 词：神经退行性疾病 肌萎缩侧索硬化 囊泡转运 外泌体 综述 

分 类 号：R741[医药卫生—神经病学与精神病学]