《生命科学》 2014, 26(7): 739-744

TDP-43在神经退行性疾病中的功能和作用

刘　丽，申景岭^*

(哈尔滨医科大学基础医学院组织学与胚胎学教研室，哈尔滨 150081)

摘　要：摘　要：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。

The function of TDP-43 in neurodegenerative disease

LIU Li， SHEN Jing-Ling^*

(Department of Histology and Embryology， Basic Medical Science College，
    Harbin Medical University， Harbin 150081， China)

Abstract: Abstract: 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.