Flipping the Switch: MeCP2-Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation.

ABSTRACT: Microglial metabolic/inflammatory reprogramming critically influences stroke outcomes, yet its mechanisms remain poorly understood. Lysine lactylation, an epigenetic modification in which lactate-derived lactyl groups modify lysine residues, regulates immune and neurological processes. Here, lysine lactylation is identified as a key link between ischemic metabolic stress and microglial dysfunction. Stroke-induced lactate accumulation drives microglial protein lactylation, which correlates with poor neurological outcomes. Proteomics identified that methyl-CpG binding protein 2 (MeCP2) is lactylated at lysine 210 (K210), enhancing its transcriptional activation of glycolytic/inflammatory genes, especially hexokinase 2 (HK2). HK2 overexpression mimics lactylation-induced pathology (mitochondr

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC12948279 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature