ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
MeCP2 Lactylation Protects against Ischemic Brain Injury by Transcriptionally Regulating Neuronal Apoptosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Fumarate Hydratase Lactylation Exacerbates Traumatic Brain Injury Pathology via Mitochondrial Dysfunction and Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate as a metabolic-epigenetic hub in neurological disorders.Metabolic brain disease · 2026Review
- Microglial Immunometabolic Remodeling After Ischemic Stroke: The Interplay Between Mitochondrial Stress and the Ischemic Microenvironment.Translational stroke research · 2026Review
- Recombinant CXCL16 reduces brain injury by modulating microglial phenotype and attenuating apoptosis in acute ischemic stroke.Scientific reports · 2026Article
- Microglia-Mediated Vascular Network Remodeling After Ischemic Stroke: An Immunovascular Repair Framework.Cells · 2026Review
- Phosphorylation-Facilitated CKB Lactylation At K11 By GCN5 Enhances Creatine Kinase Activity and Mitigates Neuronal Damage After Cerebral Ischemia-Reperfusion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aerobic exercise enhances α-tubulin lactylation and neurological recovery after ischemic stroke.Cell & bioscience · 2026Article
- GPNMB modulates neutrophil extracellular trap formation: therapeutic implications for ischemic stroke.Journal of neuroinflammation · 2026Article
- Lactylation of PTBP1 drives a pro-apoptotic positive feedback loop in microglia following oxygen-glucose deprivation/reoxygenation-induced injury.Cell death & disease · 2026Article
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Lactylation-regulated ferroptosis: mechanisms, disease associations, and therapeutic strategies.Archives of pharmacal research · 2026Review
- Metabolic-Epigenetic-Immune axis in Ischemic Stroke: Lactate-derived Lactylation as a Key Regulator.Metabolic brain disease · 2026Review
- Lactate metabolism and lactylation: Therapeutic and pre-clinical implications in neovascularization in peripheral artery disease.Journal of pharmaceutical analysis · 2026Review
- KDM5B-driven glucose metabolic reprogramming promotes enzalutamide resistance in prostate cancer via the lactate/hnRNPA1 lactylation/AR-V7 axis.Molecular cancer · 2026Article
- Flipping the Switch: MeCP2-Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- HSPA8 lactylation attenuates neuronal pyroptosis via E3 ligase-mediated NLRP3 degradation after ischemic stroke.Apoptosis : an international journal on programmed cell death · 2026Article
- HAT1 as a Lactyltransferase to Promote DNA Repair Through RPA1 Lactylation in Glioblastoma.International journal of biological sciences · 2026Article
- Integrating single-cell analysis and machine learning algorithms to explore lactylation-related molecular mechanisms and therapeutic responses in clear cell renal cell carcinoma and identifying CDT1 as a potential biomarker.Frontiers in endocrinology · 2026Article
- Lactylation in urological malignancies: emerging mechanisms and therapeutic direction.Frontiers in cell and developmental biology · 2026Review
- When metabolic enzymes meet lactylation: a bidirectional dialogue in health and disease.Frontiers in cell and developmental biology · 2026Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Lactate plays diverse roles in brain pathophysiology, including ischemic stroke. Here, the role of lysine lactylation, an epigenetic modification of lactate, in cerebral ischemia is investigated. Using a mouse model of transient middle cerebral artery occlusion, increased brain lactate levels and global protein lactylation are observed. Proteomics analysis reveals significant lactylation of non-histone proteins in the ischemic penumbra. Lactylation of MeCP2, a transcriptional regulator, is identified as a protective mechanism against stroke-induced neuronal death. Inhibition of MeCP2 lactylation through chemical or genetic manipulation increases infarct volume and aggravates neurological deficits. Mechanistically, MeCP2 lactylation at K210/K249 represses the transcription of apoptosis-associated genes, including Pdcd4 and Pla2g6, thereby attenuating neuronal apoptosis. Additionally, HDAC3 and p300 are identified as key enzymes that regulate MeCP2 lactylation post-stroke. The findings suggest that MeCP2 lactylation offers a potential therapeutic target for alleviating neuronal damage and improving stroke outcomes.
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