Lactylation of tau in human Alzheimer's disease brains.

ABSTRACT:

Introduction

Aggregation of hyperphosphorylated tau (tauopathy) is associated with cognitive impairment in patients with Alzheimer's disease (AD). In AD, a metabolic shift due to the Warburg effect results in increased lactate production. Lactate can induce a post-translational modification (PTM) on proteins that conjugates lactyl groups to lysine (K) residues, which is known as lactylation.

Methods

We analyzed lactylation of tau in control and AD brain tissue and conducted cell-based assays. In addition, we used in vitro assays to determine whether p300 catalyzed tau lactylation.

Results

Quantitative proteomics detected that tau lactylation was elevated in AD brains, with K residue at position 331 (K331) being a prominent site. Lactate induced tau lactylation, which

SUBMITTER: Zhang X 

PROVIDER: S-EPMC11851134 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature