核转录因子TDP-43的病理作用及在疾病诊疗中的应用研究进展

Research progress on the pathological effects of nuclear transcription factor TDP-43 and its application in disease diagnosis and treatment

核转录因子TAR DNA结合蛋白43(TDP-43)是一种普遍表达且在进化上高度保守的DNA/RNA结合蛋白。在生理状态下,TDP-43主要定位于细胞核、细胞质(含量不超过30%)时可发挥生理学作用,如参与mRNA的转录、剪接、翻译、转运以及维持mRNA的稳定性等,若错误定位于线粒体则发挥相应的病理作用。近年来的研究发现,除了在神经退行性疾病中发挥作用外,TDP-43还在肿瘤、男性不育和骨性关节炎(OA)等其他疾病的病理进程中起重要作用。因此,TDP-43的基因表达、亚细胞器转位、功能以及与疾病的关系越来越受到关注。本文对TDP-43的病理作用及其在疾病诊疗中的应用研究进展进行综述,以期为相关疾病的诊断及治疗提供更多帮助。

Nuclear transcription factor TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein commonly expressed and highly conserved in evolution.In physiological state,TDP-43,when localized mainly in nucleus and cytoplasm (no more than 30%),may play a physiological role,such as participating in mRNA transcription,splicing,translation,transport and maintaining the stability of mRNA,while its mislocalization in mitochondria might play a corresponding pathological role.Recent researches found that,in addition to produce a marked effect in neurodegenerative diseases,TDP-43 also plays an important role in the pathological process of tumors,male infertility,osteoarthritis (OA) and other diseases.Therefore,the gene expression,subcellular organelle translocation,function and the relationship with diseases of TDP-43 have attracted more and more attention.The research progress of pathological effects of TDP-43 has been reviewed in present paper,so as to provide more help for diagnosis and treatment of related diseases.