阿尔茨海默病中Tau蛋白聚集抑制剂的研究进展

Development of Tau aggregation inhibitor in Alzheimer's disease

近年来,以Tau蛋白作为阿尔茨海默病靶点的药物研究受到越来越多的关注。纵观国内外发展状况,基于Tau蛋白磷酸化酶的药物研发居多,部分已进入临床阶段,而关于直接抑制Tau聚集的药物研究尚处于起步阶段。从药物化学的角度,综述了目前关于小分子化合物能够有效抑制Tau蛋白异常聚集的研究进展,系统考察了这些小分子化合物的结构特征,并对其结构和功能的关系作了初步的探讨。

The microtubule-associated protein Tau aggregates into insoluble paired helical filaments （PHFs） that deposite as neurofibriUary tangles （NFTs） which may cause neurodegeneration in the brains of those with Alzheimer＇ s disease （AD） and other related tauopathies. Recently, the drug discovery targe ted on Tau protein has attracted an increasing number of researchers. In the last decade, most of the studies were focused on the approach to search for inhibitors of phosphorylation kinases, while only few put their eyes on the approach to discover direct inhibitors of Tau aggregation process. Herein, this review summarized recent advances in the discovery of small-molecule inhibitors of Tan aggregation from a me- dicinal chemistry point of view emphasizing on the structure-activity relationship.