Microtubule-associated protein tau (truncated at Aspartate 421) (TauC3)

TauC3 is a pathological, C-terminally truncated fragment of the microtubule-associated protein tau, generated by caspase-mediated cleavage at the Aspartate 421 (Asp421) residue. While normal tau protein is essential for stabilizing axonal microtubules and maintaining neuronal structure, the cleavage of tau by caspases—particularly caspase-3—results in the formation of the TauC3 species, which exhibits a significantly increased propensity for rapid self-assembly and aggregation. This fragment acts as a potent seed, promoting the formation of toxic paired helical filaments and neurofibrillary tangles that are characteristic of Alzheimer's disease and other tauopathies. In disease states, the presence of TauC3 is closely linked to synaptic loss, mitochondrial dysfunction, and the induction of neuronal apoptosis. Consequently, TauC3 is a primary target for disease-modifying therapies, including monoclonal antibodies designed to clear pathological tau and small-molecule inhibitors aimed at preventing caspase-mediated truncation.

Other names

Caspase-cleaved tauTau truncated at Aspartate 421T4C3Asp421-cleaved tauDelta-tauC-terminally truncated tau

Passive immunotherapy, inhibition of tau aggregation, protease inhibition of caspase-3, induction of autophagy for protein clearance, and targeted protein degradation.