ArticleNPJ Parkinson's disease2025
Enhanced glycolysis-derived lactate promotes microglial activation in Parkinson's disease via histone lactylation.
Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
- Exercise-induced protein lactylation: From molecular mechanisms to precision health applications.iScience · 2026Review
- H4K12 Lactylation Impairs Dopaminergic Neuron Energy Metabolism via the HIF-1α/NDUFS1 Pathway in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lactate as a metabolic-epigenetic hub in neurological disorders.Metabolic brain disease · 2026Review
- Roles of lactate and protein lactylation in neurogenesis and neurodegenerative disease.Journal of translational medicine · 2026Review
- Review
- A Lactate-H4K12la-HDAC1 epigenetic axis governs microglial state transitions during experimental autoimmune encephalomyelitis in female mice.Nature communications · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Modeling stimulus-induced stress responses in microglia-like cells using a commercial iPSC-dCas9-KRAB line.Stem cell research · 2026Article
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Exerkine-Mediated Regulation of the NLRP3 Inflammasome in Neuroprotection: Mechanistic Insights and the Role of Exercise.Molecular neurobiology · 2026Review
- Brain-muscle axis regulation of neuroinflammation and sarcopenia in Parkinson's disease: the bridging role of lactylation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Enhanced Glycolysis-Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Histone H3K18 Lactylation Contributes to Perioperative Neurocognitive Disorder Through Immune Checkpoint Lymphocyte Activation Gene 3 Mediated Microglial Pyroptosis.CNS neuroscience & therapeutics · 2026Article
- Lactate-fueled H3K18 lactylation sustains ΔNp63α-dependent self-renewal in limbal epithelial stem cells.The Journal of biological chemistry · 2026Article
- Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.Clinical epigenetics · 2026Review
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- Early GPR81/MCT1 rise and late lactate-NAD(H) Build-up in an LPS model of PD.Metabolic brain disease · 2026Article
- MPTP and rotenone cause dopaminergic neuronal death by increasing DDIT4 promoter lactylation.Acta pharmacologica Sinica · 2026Article
- Data Resources and Computational Methods for Lactylation Site Prediction: A Mini-Review.International journal of molecular sciences · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The switch from oxidative phosphorylation to glycolysis is crucial for microglial activation. Recent studies highlight that histone lactylation promotes macrophage homeostatic gene expression via transcriptional regulation, but its role in microglia activation in Parkinson's disease (PD) remains unclear. Here, we demonstrated that inhibiting glycolysis with 2-deoxy-D-glucose alleviates microgliosis, neuroinflammation and dopaminergic neurons damage by reducing lactate accumulation in PD mice. Notably, we observed a marked increase in histone lactylation, particularly H3K9 lactylation, in microglia in the substantia nigra of PD mice. Mechanistically, CUT&Tag and Chip-qPCR analyses revealed that H3K9 lactylation enriched at the SLC7A11promoter and activated its expression. Importantly, inhibiting SLC7A11 by sulfasalazine mitigated microglia-mediated neuroinflammation and improved motor function in PD mice. Moreover, we found that lactate-induce histone lactylation is dependent on P300/CBP. Collectively, our findings demonstrate that glycolysis-derived lactate promotes microglial activation via histone lactylation and provide a potential therapeutic strategy for PD.
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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.