Microtubule-associated protein tau, 4-repeat isoform (Tau (4R tau))

4-Repeat tau protein (4R tau) is a major neuronal isoform of the microtubule-associated protein tau (MAPT), generated by alternative mRNA splicing that includes all four microtubule-binding repeat domains near the C-terminus. The 4R tau isoform binds and stabilizes microtubules in neurons more effectively than the 3-repeat isoforms and plays a crucial role in cytoskeletal organization, axonal transport, and neuronal development. Imbalance in 4R/3R tau expression or aggregation of 4R tau is a hallmark of several neurodegenerative disorders collectively known as tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and certain forms of frontotemporal dementia. Pathological aggregation leads to the formation of paired helical and straight filaments with various disease-specific conformer structures. Pharmacological strategies targeting 4R tau primarily aim to prevent aggregation, promote clearance, or modulate splicing to restore isoform balance. Therapies face significant challenges due to the essential physiological roles of tau and the complexity of tau-related pathologies[1][2][4][5][6][7][8][9].

Other names

4R tauFour-repeat tauMAPT (4R isoform)Tau protein (4-repeat isoform)

Inhibition of tau aggregation (e.g., methylene blue, CLR01); Immunological clearance of pathological tau (anti-tau antibodies); Modulation of microtubule stability