Arai Tetsuaki, Hosokawa Masato, Hasegawa Masato, Akiyama Haruhiko, Asada Takashi
Department of Psychiatry, Graduate School of Comprehensive Human Sciences, University of Tsukuba.
Seishin Shinkeigaku Zasshi. 2011;113(6):574-83.
The TAR DNA-binding protein Mr 43 kDa (TDP-43) is a major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer's disease, forming a group of TDP-43 proteinopathies. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role in the pathological process. Understanding the mechanism of phosphorylation and truncation of TDP-43, and aggregate formation, may be crucial to clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapies.
43 kDa的TAR DNA结合蛋白（TDP - 43）是肌萎缩侧索硬化症（ALS）和额颞叶痴呆（现称为FTLD - TDP）所特有的tau蛋白阴性和泛素阳性包涵体的主要成分。在多种其他神经退行性疾病如阿尔茨海默病中也报道了并发的TDP - 43病理改变，形成了一组TDP - 43蛋白病。累积的TDP - 43的特征是磷酸化和片段化。FTLD - TDP的病理亚型与磷酸化TDP - 43 C末端片段的免疫印迹模式之间存在密切关系。这些结果表明，累积的TDP - 43的蛋白水解加工可能在病理过程中起重要作用。了解TDP - 43的磷酸化和截断机制以及聚集体形成，对于阐明TDP - 43蛋白病的发病机制和开发有效的治疗方法可能至关重要。
