Tau Protein Aggregation in Alzheimer's Disease: Recent Advances in the Development of Novel Therapeutic Agents

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.