神经退行性疾病中的TDP-43蛋白聚集和相变

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...

Protein Aggregation and Phase Separation in TDP-43 Associated Neurodegenerative Diseases

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 of ALS.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.