Hexameric Aggregation Nucleation Core Sequences and Diversity of Pathogenic Tau Strains.

ABSTRACT: Tau aggregation associates with multiple neurodegenerative diseases including Alzheimer's disease and rare tauopathies such as Pick's disease, progressive supranuclear palsy, and corticobasal degeneration. The molecular and structural basis of tau aggregation and related diverse misfolded tau strains are not fully understood. To further understand tau-protein aggregation mechanisms, we performed systematic truncation mutagenesis and mapped key segments of tau proteins that contribute to tau aggregation, where it was determined that microtubule binding domains R2 and R3 play critical roles. We validated that R2- or R3-related hexameric PHF6 and PHF6* peptide sequences are necessary sequences that render tau amyloidogenicity. We also determined that the consensus VQI peptide sequence is not

SUBMITTER: Wu L 

PROVIDER: S-EPMC9784471 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature