基于tau蛋白的阿尔茨海默病药物研发方法概述

The overview of techniques of AD drug developments targeting tau protein

阿尔茨海默病(Alzheimer′s disease,AD)是一种表现为记忆、认知障碍并伴随焦虑情绪的神经退行性疾病。由淀粉样β蛋白组成的老年斑和tau蛋白形成的神经纤维缠结是阿尔茨海默病主要的分子病理特征。Tau病理是阿尔茨海默病发病机制的主要假说之一,成为药物研发者的关注重点。本文就当前以tau蛋白为靶点的阿尔茨海默病药物研发进行了分析,在分子、细胞、整体动物以及计算机辅助药物研发水平上总结了临床前实验中常用的研究模型及评价方法,概述不同模型的利弊并展望其未来发展方向。

Alzheimer′s disease(AD)is a neurodegenerative disease with memory and recognition defects and anxiety.The senile plaque formed by amyloidβ-protein(Aβ)and neurofibrillary tangles containing tau protein are the main pathological characteristics.Tau hypothesis is one of the most accepted AD mechanisms.As most potential drugs targeting Aβfailed in clinical trials recently,tau protein attracts much more attention.Based on the recent studies on AD drug developments,this review summarizes the models and techniques used in molecular,cellular,mouse,and computational researches.We further evaluate the advantages and disadvantages of each model and prospect the future directions.