ArticleCell death & disease2025
H3K14 lactylation exacerbates neuronal ferroptosis by inhibiting calcium efflux following intracerebral hemorrhagic stroke.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Histone H4K5 lactylation-driven feedback loop modulates glycerol-linked immunosuppressive activity of tumor-associated T regulatory cells.Signal transduction and targeted therapy · 2026Article
- Ischemic Stroke and Traumatic Brain Injury: Epidemiology, Molecular Pathways, and Emerging Therapies.MedComm · 2026Review
- Acetylation-like H2BK109Q attenuates acute brain injury and preserves axon-myelin integrity after intracerebral hemorrhage.CNS neuroscience & therapeutics · 2026Article
- Lactylation and regulated cell death: the substrate defines the outcome.Apoptosis : an international journal on programmed cell death · 2026Article
- Lactylation and N6-Methyladenosine RNA modification in neuropsychiatric sequelae after intracerebral hemorrhage: a hypothesis-generating metabolic-glial-circuit framework.Molecular biology reports · 2026Review
- Lactate as a metabolic-epigenetic hub in neurological disorders.Metabolic brain disease · 2026Review
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Lactylation-regulated ferroptosis: mechanisms, disease associations, and therapeutic strategies.Archives of pharmacal research · 2026Review
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Lactate modulates microglial M2 polarizationJournal of translational internal medicine · 2026Article
- Lactylation‑mediated ferroptosis: A novel mechanism and therapeutic prospects in human diseases (Review).International journal of molecular medicine · 2026Review
- Lactate: elucidating its indispensable role in human health.Molecular cancer · 2026Review
- Lactate and lactylation in sepsis: regulation of immune-metabolic crosstalk and organ injury.Frontiers in immunology · 2026Review
- Lactylation at the crossroads of metabolism and epigenetics in neuroinflammation.Frontiers in immunology · 2026Review
- Dual roles of lactate and lactylation modification in the nervous system: neuroprotection and neuroinjury.Frontiers in aging neuroscience · 2026Review
- Hematoma-driven immuno-epigenetic remodeling after intracerebral hemorrhage: cell-type-specific mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Review
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Authors and funding
20 authors.
Funding
Abstract
Inhibiting neuronal ferroptosis is essential for mitigating neural damage and enhancing recovery in central nervous system (CNS) disorders, including intracerebral hemorrhagic stroke (ICH). Lactate accumulation correlates with ICH severity, yet the role of lactate-derived histone lactylation, a novel epigenetic modification, in ferroptosis and its mechanisms is not fully understood. In this study, we aimed to investigate the role of histone lactylation on neuronal ferroptosis in ICH models, both in vitro and in vivo. We discovered elevated lactate and histone lactylation post-ICH in mice, with a significant increase in H3K14la during the early stages of ferroptosis in hemin-challenged primary cortical neurons. Pharmacological or genetic inhibition of H3K14la by targeting lactate dehydrogenase (LDH) enzyme activity effectively suppressed neuronal ferroptosis. We further identified p300/CBP and class I histone deacetylases (HDACs) as the key modifiers of H3K14la in this process. Through chromatin immunoprecipitation-sequencing and RNA-sequencing (RNA-seq) in hemin-treated neurons, we pinpointed the Ca
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.