Tau蛋白与分子伴侣的相互作用

The interactions between Tau protein and molecular chaperones

作为老年人中最常见的一种神经退行性疾病,阿尔茨海默病(Alzheimer’s disease,AD)发病机制一直未明确,多种因素共同作用导致该病的发生和发展。AD患者脑内的一大关键病理特征是异常磷酸化的Tau蛋白错误折叠、聚集形成的神经纤维缠结。作为调节蛋白质构象的重要分子,分子伴侣可以与Tau蛋白发生相互作用,对Tau蛋白的聚集产生一定的影响。本文主要介绍了4种与Tau蛋白相互作用的分子伴侣,包括HSP70、HSP90、HSP40和sHSP,并从结构生物学角度详细描述了它们互作的分子机制。本文进一步展望了以HSP或其相关分子为靶标的AD药物的研发前景,为AD的防治研究提供新思路。

Alzheimer’s disease(AD) is the most common neurodegenerative disease happened in elderly,with unclear pathogenesis. Several factors work together to lead to the occurrence and development of the disease. One critical pathological characteristic of AD is the neurofibrillary tangles consisting of hyperphosphorylated Tau protein via misfolding and aggregating. As an important type of molecules that regulate protein conformation, molecular chaperones can interact with Tau protein and play a certain role in the aggregation of Tau protein. This review mainly introduces four significant molecular chaperones that interact with Tau protein, including HSP70, HSP90, HSP40 and sHSP. Their interaction mechanisms are described in term of structure biology. This review prospects the potential of HSP or related molecules as the target for AD drug design as well, providing new strategies for future researches on the prevention and treatment of AD.