Structure and Mechanism of Action of Tau Aggregation Inhibitors

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

Journal Name: Current Alzheimer Research

Volume 11 , Issue 10 , 2014

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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.

Keywords: Alzheimer’s disease, aggregation, neurofibrillary tangle, paired helical filaments, tau.

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Article Details

Year: 2014
Published on: 28 November, 2014
Page: [918 - 927]
Pages: 10
DOI: 10.2174/1567205011666141107150331
Price: $65

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