神经退行性疾病中的TDP-43蛋白聚集和相变

• 作 者: 石丽君 徐安琪 朱笠
• 机 构: 中国科学院生物物理研究所,脑与认知科学国家重点实验室,北京100101;西北农林科技大学动物医学院,杨陵712100;中国科学院生物物理研究所,脑与认知科学国家重点实验室,北京100101;中国科学院
• 出 处: 生物化学与生物物理进展
• 发表日期: 2022年1期
• 关键词: TDP-43 proteinopathy amyotrophic lateral sclerosis (ALS) frontotemporal lobar de

随着全球老龄化人口的急剧增加,神经退行性变已经成为危害公共健康的主要疾病.在神经退行性疾病(肌萎缩侧索硬化症(ALS)、额颞叶变性病(FTLD)和阿尔茨海默病(AD)等)患者脑组织中均能观察到蛋白质聚集形成的包涵体,其中TAR DNA结合蛋白43 (TDP-43)是主要成分之一.目前已发现多个TDP-43基因突变与家族性ALS密切相关TDP-43属RNA/DNA结合蛋白,参与细胞内多种RNA代谢过程,它可以在细胞核和细胞质之间穿梭,通过相变诱导胞质和核质包涵体的形成.本文简要总结了TDP-43在体内和体外聚集以及发生相变的研究进展.理解TDP-43的异常相变将有助于寻找神经退行性疾病的潜在治疗靶点.“,”With the aging population increasing worldwide,neurodegenerative diseases are becoming a major public health crisis.TAR DNA-binding protein 43 (TDP-43) is one of the major components in the inclusion bodies containing aggregated proteins in affected patients with several types of neurodegenerative diseases,including amyotrophic lateral sclerosis (ALS),frontotemporal lobar degeneration (FTLD) and Alzheimer\'s disease (AD).A large number of mutations in TDP-43 have been identified in familial cases ofALS.TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism,it shuttles between nucleus and cytoplasm,and undergoes phase transition to induce cytoplasmic and nucleoplasmic inclusion formation.Here,we summarized the recent advances in our understanding of protein aggregation and phase transition of TDP-43 in vitro and in vivo.Understanding the aberrant transition of TDP-43 will help identify potential therapeutic targets for neurodegenerative diseases.