tau-targeting PROTAC

A tau-targeting PROTAC (proteolysis-targeting chimera) is a class of heterobifunctional small molecules designed to selectively degrade pathological tau protein, a key driver of neurodegeneration in Alzheimer's disease and other tauopathies. These chimeric molecules consist of a tau-binding ligand linked to an E3 ubiquitin ligase-recruiting ligand, such as cereblon (CRBN) or von Hippel-Lindau (VHL). By bringing the target tau protein into close proximity with the E3 ligase, the PROTAC facilitates polyubiquitination of tau, marking it for rapid degradation via the intracellular ubiquitin-proteasome system. This catalytic mechanism allows a single PROTAC molecule to degrade multiple copies of tau, offering a highly efficient therapeutic approach to clear toxic tau aggregates and hyperphosphorylated tau species from neurons.

Other names

p-tau-PROTACtau degrader PROTACtau-directed PROTACtau-targeted PROTAC