微管相关蛋白Tau蛋白及Tau病的研究进展

Advances in microtubule-associated proteins tau protein and tauopathy

Tau蛋白是微管相关蛋白家族的主要成员,其磷酸化水平的增高与多种中枢神经系统疾病密切相关,如阿尔茨海默病(Alzeimer's disease,AD)、癫痫、额颞叶痴呆、皮质基底节变性(corticobasal degeneration,CBD)、进行性核上性麻痹(progressive supranuclear palsy,PSP)、朊蛋白病等。Tau病是以异常磷酸化Tau蛋白聚集为病理特点的年龄相关性神经变性病。Tau病根据微管相关蛋白Tau(microtubule-associated proteins tau,MAPT)基因剪切不同分为6种同型异构体,外显子9,10、11、12各编码一个微管结合模序氨基酸重复序列,有外显子10编码氨基酸序列的Tau蛋白异构体为4R,其他的异构体为3Ro皮克病(Pick's disease,PiD)中3R占优势,而皮质基底节变性和进行性核上性麻痹中4R占优势,根据MAPT中基因突变的位置,额颞叶痴呆FTLD-tau可以出现3R、4R或二者均有。本文综述了近年来在Tau蛋白及Tau病相关领域的研究进展。

Tau protein is a main member of microtubule-associated proteins, hyperphosphorylation of tau is associated with many central nervous system diseases, such as Alzeimer＇s disease, epilepsy, frontal-temporal dementia, corticobasal degeneration, progressive supranuclear palsy, prion diseases and so on. Tauopathies are age-related neurodegenerative diseases that are characterized by the presence of aggregates of abnormally phosphorylated tau. Tauopathies can be classified into 6 isoforms according to the alternative splicing of MAPT. Exons 9, 10, 11, and 12 each encodes a microtubule binding motif. Isoforms that include exon 10 are commonly referred to as four-repeat or 4R tau isoforms while those that exclude exon 10 are referred to as threerepeat or 3R tau isoforms. 3R tau predominates in Pick＇s disease （PiD）, whereas 4R tau predominates in corticobasal degeneration （CBD） and progressive supranuclear palsy （PSP）. Depending upon the specific mutation in MAPT, familial FTLD-tau have 3R, 4R or a combination of 3R and 4R tau. This article provides an overview of tau structure, functions, and its involvement in neurodegenerative diseases.