TauAutac-3

TauAutac-3 (TA-3) is a novel, small-molecule autophagy-targeting chimera (AUTAC) designed for the selective degradation of tau protein to treat Alzheimer's disease. Developed through a collaboration involving Soonchunhyang University, Yonsei University, Gachon University, and Dalim Fromtech, TA-3 is synthesized by conjugating leucomethylene blue (a tau-binding warhead) to an autophagic degradation tag (Autac) via a chemical linker. TA-3 selectively binds to both monomeric and oligomeric forms of tau, promoting their clearance through the autophagy-lysosomal pathway. In preclinical models, including 6xTg mice and patient-derived iPSC neuronal cells, TA-3 treatment significantly reduced tau and amyloid-beta accumulation, alleviated tau-mediated lysosomal stress and neuroinflammation, and reversed cognitive and behavioral deficits.