Major research in Alzheimer’s disease (AD) related to disease-modifying agents is concentrated on
pharmacological approaches related to diagnostic markers, neurofibrillary tangles and amyloid plaques. Although
most studies focus on anti-amyloid strategies, investigations on tau protein have produced significant advances in
the modulation of the pathophysiology of several neurodegenerative diseases. Since the discovery of phenothiazines
as tau protein aggregation inhibitors (TAGIs), many additional small molecule inhibitors have been discovered
and characterized in biological model systems, which exert their interaction effects by covalent and noncovalent
means. In this paper, we summarize the latest advances in the discovery and development of tau aggregation
inhibitors using a specialized approach in their chemical classes. The design of new TAGIs and their encouraging
use in in vivo and clinical trials support their potential therapeutic use in AD.
Keywords: Alzheimer`s disease, tau protein, aggregation inhibitors, neurodegeneration, phenothiazines, molecule inhibitors.
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