TDP-43在帕金森病发病机制中作用的研究进展

Advances in Research on Role of TDP-43 in Pathogenesis of Parkinson′s Disease

帕金森病(PD)是一种常见的神经系统退行性疾病,其病理特征为黑质致密部多巴胺能神经元缺失以及残留神经元中出现包涵体,主要为路易小体(LB)。近年来,TAR DNA结合蛋白43(TDP-43)被发现是神经退行性疾病的病理学标记蛋白。TDP-43是PD患者脑切片中LB的主要成分,在PD发病机制中发挥重要作用。TDP-43可能通过增强α-突触核蛋白的毒性,促进Tau蛋白的过度磷酸化,诱导线粒体功能障碍,抑制自噬,增加神经炎症等机制使多巴胺能神经元变性丢失,导致PD发病。

Parkinson′s Disease(PD)is a common neurodegenerative disease with pathological features of the absence of dopaminergic neurons in the dense substantia nigra and the presence of inclusion bodies in residual neurons,mainly Lewy′s body(LB).In recent years,TAR DNA-binding protein 43(TDP-43)has been found to be a pathological marker protein for neurodegenerative diseases.And studies have shown that TDP-43 is the main component of LB in brain slices of PD patients,and its role in the pathogenesis of PD deserves attention.It may cause degeneration and loss of dopaminergic neurons,leading to the onset of PD by promoting the excessive Tau protein phosphorylation,enhancing the toxicity ofα-synuclein,inducing mitochondrial dysfunction,inhibiting autophagy,increasing neuroinflammation and other mechanisms.