Microtubule-associated protein tau fibril (Tau fibril (commonly "Tau" for the protein; isoforms such as PHF for paired helical filament))

Tau fibrils are insoluble, β-sheet-rich aggregates formed from the tau protein, which is normally a soluble, intrinsically disordered microtubule-associated protein essential for stabilizing neuronal microtubules and promoting axonal transport[2][5]. In disease states, tau undergoes abnormal modifications (notably hyperphosphorylation) that disrupt its normal function and promote aggregation into fibrils with amyloid characteristics[2][4][5]. These tau fibrils then accumulate within neurons to form neurofibrillary tangles, a hallmark of Alzheimer’s disease and other tauopathies[2][3][5]. Cryo-EM and NMR studies have shown that the rigid fibril core is formed by repeats in the microtubule-binding region of tau, with its structure varying between disease types and environmental conditions[1][2][3]. Drugs in development aim to disaggregate tau fibrils or prevent their formation, but significant therapeutic and safety challenges remain[6]. Tau fibrils are not a canonical receptor, enzyme, transporter, or gene product, but their unique structural and pathological characteristics make them a well-established therapeutic target in neurodegenerative disease drug discovery[2][3][6].

Other names

Tau protein fibrilAmyloid tau fibrilPHF (Paired helical filament)NFTs (Neurofibrillary tangles, comprised of tau fibrils)Tau aggregates

Disaggregation of tau fibrils (e.g. EGCG binds to sites within the fibril and disrupts its structure)[6]; Inhibition of tau aggregation; Promotion of tau clearance; Immunotherapy targeting pathological tau for destruction by immune cells