The ordered assembly of tau is the gain-of-toxic function that causes human tauopathies.
A pathological pathway leading from soluble to insoluble and filamentous tau underlies human tauopathies. This ordered assembly causes disease and is the gain-of-toxic function. It involves the transition from an intrinsically disordered monomer to a highly structured filament. Based on recent findings, one can divide the ordered assembly into propagation of pathology and neurodegeneration. Short tau fibrils constitute the major species of seed-competent tau in the brains of mice transgenic for human P301S tau. The molecular species of aggregated tau that are essential for neurodegeneration remain to be identified.
MRC Laboratory of Molecular Biology, Cambridge United Kingdom. Electronic address: mg@mrc-lmb.cam.ac.uk.
Michel
M
Goedert
D000682:Amyloid; D000818:Animals; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000473:pathology; D010766:Phosphorylation; D066329:Protein Aggregates; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
D000682:Amyloid; D066329:Protein Aggregates; D016875:tau Proteins
Alzheimer's disease; Cell-to-cell spreading; Prion-like; Propagation of pathology; Protein strains; Tau; Tauopathy; Toxicity