Mechanistic basis of phenothiazine‐driven inhibition of Tau aggregation

Abstract

Blues brothers: Aggregation of the Tau protein is a key event in Alzheimer's disease and Tau aggregation inhibitors are important as potential drugs. Phenothiazines, such as methylene blue and its azure derivatives, have a unique mechanism, specifically modifying the Tau cysteine residues. The modification keeps Tau in a monomeric disordered conformation preventing the formation of filaments and their toxic precursors.