Regulatory mechanisms of tau protein fibrillation under the conditions of liquid-liquid phase separation.

ABSTRACT: One of the hallmarks of Alzheimer's disease and several other neurodegenerative disorders is the aggregation of tau protein into fibrillar structures. Building on recent reports that tau readily undergoes liquid-liquid phase separation (LLPS), here we explored the relationship between disease-related mutations, LLPS, and tau fibrillation. Our data demonstrate that, in contrast to previous suggestions, pathogenic mutations within the pseudorepeat region do not affect tau441's propensity to form liquid droplets. LLPS does, however, greatly accelerate formation of fibrillar aggregates, and this effect is especially dramatic for tau441 variants with disease-related mutations. Most important, this study also reveals a previously unrecognized mechanism by which LLPS can regulate the rate of fibr

SUBMITTER: Boyko S 

PROVIDER: S-EPMC7749306 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature