Mechanistic Basis of Phenothiazine-Driven Inhibition of Tau Aggregation

摘要

Alzheimer's disease (AD) is the most widespread dementia syndrome showing progressive presence of abundant deposits of extracellular senile β-amyloid polypeptide (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) consisting of Tau protein. Tau protein is an intrinsically disordered protein that is abundant in neuronal axons where it promotes and stabilizes microtubule assembly. With progression of AD, Tau aggregates and accumulates into NFTs. As there is still no causative treatment or cure for AD and other tauopathies, Tau-based research aims to reveal the pathological consequences of amyloid formation and to implement new therapeutic strategies. In this effort, identification of inhibitors of tau aggregation as potential disease-modifying drugs and investigation of their mode of action play an important role.