ArticleCommunications biology2024
Therapeutic potential of microglial SMEK1 in regulating H3K9 lactylation in cerebral ischemia-reperfusion.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The trial behind it
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Who cites it
27 citing papers in PubMed.
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- Microglial Mitochondrial Dysfunction: The Storm Center of Post-Stroke Neuroinflammation.CNS neuroscience & therapeutics · 2026Review
- Interplay between ischemia-reperfusion and metabolic reprogramming.Apoptosis : an international journal on programmed cell death · 2026Review
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Erbin Confers Neuroprotection against Cerebral Ischemia-Reperfusion Injury in Mice via MAPK Pathway Inhibition.eNeuro · 2026Article
- Metabolic-Epigenetic-Immune axis in Ischemic Stroke: Lactate-derived Lactylation as a Key Regulator.Metabolic brain disease · 2026Review
- Hexokinase 3 promoted cytokine production of monocytes by targeting metabolic reprogramming and histone lactylation in sepsis.Clinical epigenetics · 2026Article
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Uncovering the metabolic-epigenetic links between gene expression and stroke: insights from lactylation pathway MR study.Neurological research and practice · 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
- Microglia Mitochondrial Metabolism in Neurological Diseases.Molecular neurobiology · 2026Review
- Lactylation at the crossroads of metabolism and epigenetics in neuroinflammation.Frontiers in immunology · 2026Review
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
- Lactylation Modification: From Basic Biological Process to Clinical Cardiovascular Diseases.Research (Washington, D.C.) · 2026Review
- Histone lactylation-mediated glycolysis-ferroptosis axis in neurological diseases.Frontiers in molecular neuroscience · 2026Review
- β-Caryophyllene protects against ischemic stroke by inhibiting H3K9 and H3K18 lactylation-mediated cellular pyroptosis.Frontiers in pharmacology · 2026Article
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Review
- How lactate and lactylation shape the immunity system in atherosclerosis (Review).International journal of molecular medicine · 2025Review
- Glucose Metabolism, Lactate, Lactylation and Alzheimer's Disease.Aging and disease · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Acute ischemic stroke (AIS) triggers immune responses and neuroinflammation, contributing to brain injury. Histone lactylation, a metabolic stress-related histone modification, plays a critical role in various diseases, but its involvement in cerebral ischemia remains unclear. This study utilized a transient middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen-glucose deprivation/reoxygenation (OGD/R) model to investigate the role of microglial histone lactylation in ischemia-reperfusion injury. Lactate overload post-AIS increased histone lactylation, while reduced SMEK1 expression in microglia correlated with elevated lactate and neuroinflammation. Microglia-specific SMEK1 deficiency enhanced lactate production by inhibiting the pyruvate dehydrogenase kinase 3-pyruvate dehydrogenase (PDK3-PDH) pathway, increasing H3 lysine 9 lactylation (H3K9la), activating Ldha and Hif-1α transcription, and promoting glycolysis. SMEK1 overexpression improved neurological recovery in ischemic mice. This study highlights SMEK1 as a novel regulator of histone lactylation and a potential therapeutic target for mitigating neuroinflammation and enhancing recovery after AIS.
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Registered trials
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