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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 nuclear protein TAR DNA / RNA Binding Protein 43 (TDP-43) is currently considered as a disease of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) Neutrophil marker protein. In the central nervous system, TDP-43, as an essential transcriptional regulator, participates in splicing of mRNA precursors, maintaining RNA homeostasis and trafficking. In transgenic rodent models that mutate and overexpress TDP-43, injured neurons exhibit ubiquitination of TDP-43 in nuclei and cytoplasm, phosphorylation and aggregation, and changes in cell cycle progression. Here, we mainly focus on the research progress of animal models of neurodegenerative diseases based on the mutation or overexpression of TDP-43, and discuss the pathogenesis, pathological changes and treatment methods.