Tau蛋白聚集抑制剂的结构及作用机制

Title:Structure and Mechanism of Action of Tau Aggregation Inhibitors

Volume: 11 Issue: 10

Author(s): Katryna Cisek, Grace L. Cooper, Carol J. Huseby and Jeff Kuret

Affiliation:

关键词: 阿尔茨海默病，聚集，神经元纤维缠结，成对螺旋细丝，tau蛋白

摘要: Since the discovery of phenothiazines as tau protein aggregation inhibitors, many additional small molecule inhibitors of diverse chemotype have been discovered and characterized in biological model systems. Although direct inhibition of tau aggregation has shown promise as a potential treatment strategy for depressing neurofibrillary lesion formation in Alzheimer’s disease, the mechanism of action of these compounds has been unclear. However, recent studies have found that tau aggregation antagonists exert their effects through both covalent and non-covalent means, and have identified associated potency and selectivity driving features. Here we review small-molecule tau aggregation inhibitors with a focus on compound structure and inhibitory mechanism. The elucidation of inhibitory mechanism has implications for maximizing on-target efficacy while minimizing off-target side effects.

Cite this article as:

Katryna Cisek, Grace L. Cooper, Carol J. Huseby and Kuret Jeff, Structure and Mechanism of Action of Tau Aggregation Inhibitors, Current Alzheimer Research 2014; 11 (10) . https://dx.doi.org/10.2174/1567205011666141107150331