A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy.

ABSTRACT: Tau acetylation has recently emerged as a dominant post-translational modification (PTM) in Alzheimer's disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule (MT)-binding region (MTBR), suggesting acetylation could regulate both normal and pathological tau functions. Here, we combined biochemical and cell-based approaches to uncover a dual pathogenic mechanism mediated by tau acetylation. We show that acetylation specifically at residues K280/K281 impairs tau-mediated MT stabilization, and enhances the formation of fibrillar tau aggregates, highlighting both loss and gain of tau function. Full-length acetylation-mimic tau showed increased propensity to undergo seed-dependent aggregation, revealing a potential role

SUBMITTER: Trzeciakiewicz H 

PROVIDER: S-EPMC5347034 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature