Differential Binding and Conformational Dynamics of Tau Microtubule-Binding Repeats with a Preformed Amyloid-β Fibril Seed.

ABSTRACT: Both senile plaques formed by amyloid-β (Aβ) and neurofibrillary tangles (NFTs) comprised of tau are pathological hallmarks of Alzheimer's disease (AD). The accumulation of NFTs better correlates with the loss of cognitive function than senile plaques, but NFTs are rarely observed without the presence of senile plaques. Hence, cross-seeding of tau by preformed Aβ amyloid fibril seeds has been proposed to drive the aggregation of tau and exacerbate AD progression, but the molecular mechanism remains unknown. Here, we first identified cross-interaction hotspots between Aβ and tau using atomistic discrete molecular dynamics simulations (DMD) and confirmed the critical role of the four microtubule-binding repeats of tau (R1-R4) in the cross-interaction with Aβ. We further investigated the bind

SUBMITTER: Song Z 

PROVIDER: S-EPMC10119806 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature