TDP-43在神经退行性疾病中的功能和作用

The function of TDP-43 in neurodegenerative disease

核蛋白TAR DNA/RNA结合蛋43(TDP-43)目前被认为是肌萎缩侧索硬化症(amyotrophic lateral sclerosis,ALS)、额颞叶变性(frontotemporal lobar degeneration,FTLD)等神经退行性疾病的病理学标记蛋白。在中枢神经系统中,TDP-43作为必要的转录调控因子,参与mRNA前体的剪接,维持RNA稳态和运输。在突变和过表达TDP-43的转基因啮齿类动物模型中,受损伤的神经元呈现出胞核和胞质中TDP-43泛素化、磷酸化聚集,以及细胞周期进程的改变。在此,着重阐述基于TDP-43突变或过表达建立神经退行性疾病动物模型的研究进展,探讨其发病机制、病理学改变及治疗方法。

Nuclear protein TAR DNA/RNA binding protein 43 （TDP-43） is recognized as a pathological marker protein of amyotrophic lateral sclerosis （ALS） and frontotemporal lobar degeneration （FTLD）. It is identified as a regulator of essential transcriptional events in the CNS, which is involved in pre-mRNA splicing, RNA stability and transport. In affected neurons of transgenic rodent models with TDP-43 mutation or overexpression, nuclear and cytoplasmic TDP-43 aggregates with ubiquitination or phosphorylation, and cell cycles also alterate. Here research progress on transgenic rodent models made by TDP-43 mutation or overexpression is reviewed to explore molecular mechanisms, pathological changes and new therapies for neurodegenerative disease.