TDP-43蛋白翻译后修饰的病理学功能  

The pathological roles of posttranslational modifications on TDP-43

作　　者：姚潇 杜海宁[1] YAO Xiao;DU Haining(College of Life Sciences,Wuhan University,Wuhan 430072,China)

机构地区：[1]武汉大学生命科学学院,武汉430072

出　　处：《生命的化学》2020年第8期1387-1394,共8页Chemistry of Life

基　　金：国家重大科学研究计划(2013CB910700);武汉市应用基础前沿项目(2020020601012225)。

摘　　要：很多神经退行性疾病患者的神经元和胶质细胞中都可以发现异常的蛋白质聚集。在额颞叶变性(frontotemporal lobar degeneration,FTLD)和肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)中,TAR结合蛋白43(TAR DNA-binding protein 43,TDP-43)是主要的异常聚集蛋白之一。这些TDP-43蛋白的病理性包涵体上往往存在着各种蛋白质翻译后修饰,例如磷酸化、泛素化、乙酰化修饰等。TDP-43蛋白的过度磷酸化修饰以及泛素化修饰被发现广泛存在于ALS和FTLD患者体内,而该蛋白质特定位点的乙酰化修饰也可以促进TDP-43蛋白的聚集,与ALS发病紧密相关。本文主要就近些年来TDP-43蛋白上发现的蛋白质翻译后修饰作一综述,为将来全面阐释该类型的致病机制提供一些理论基础。A large amount of neurodegenerative diseases are associated with aberrant protein aggregation in patient neuron and glial cells.It has been well-known that TAR DNA-binding protein(TDP-43)is one of the major proteins aggregated in the patients of frontotemporal lobar degeneration(FTLD)and amyotrophic lateral sclerosis(ALS).These TDP-43 pathological inclusions frequently bear various posttranslational modifications,such as phosphorylation,ubiquitination and acetylation.Hyperphosphorylated TDP-43 as well as ubiquitinated forms of TDP-43 were widely found in ALS and FTLD patients,whereas acetylated TDP-43 on certain lysine residues was also found in ALS patients,which is linked to TDP-43 proteinopathy.This review summarized so-far identified posttranslational modifications on TDP-43,which may shed light on extensively understanding TDP-43-associated pathological mechanisms.

关 键 词：ALS TDP-43 磷酸化 泛素化 乙酰化 

分 类 号：R741[医药卫生—神经病学与精神病学]