ArticleThe journal of headache and pain2025
The lactylation-immune regulatory axis: a potential therapeutic target for migraine prevention and treatment.
Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Unraveling the Cross-Tissue Neuroimmune-Vascular Genetic Architecture of Migraine Using Integrated Multi-Omics, Single-Cell, and Spatial Transcriptomics: Prioritizing T-Cell Regulatory Networks and Peripheral Targets.International journal of molecular sciences · 2026Article
- Causal Effects and Single-Cell Microenvironmental Implications of Germline Variant-Regulated Lactylation-Related Pro-Oncogenic Genes in Colorectal Cancer.Human mutation · 2026Article
- The emerging role of epigenetic regulation in pain sensitization associated with headache disorders.The journal of headache and pain · 2025Review
- Insights into the lactylation-immune regulatory axis as a mechanistic bridge in migraine pathophysiology.The journal of headache and pain · 2025Article
- A single-cell multi-omics framework identifies immune cell drivers of migraine and repurposable therapeutics.The journal of headache and pain · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
backgroundMigraine is a debilitating neurological disorder. Emerging evidence suggests that metabolic dysregulation and immune dysfunction contribute to migraine pathogenesis while the molecular mechanisms linking these processes remain unclear. Lactylation may serve as a crucial integrator of metabolic and immune signals in migraine.
methodsWe performed a comprehensive multi-omics Mendelian randomization study integrating DNA methylation, gene expression, and protein abundance data with genome-wide association studies on migraine. Summary-data-based Mendelian randomization, Bayesian colocalization, and two-sample MR analyses were conducted to identify lactylation-related genes causally associated with migraine. We further explored immune cell mediation using genetic data from 731 immune phenotypes and validated findings through single-cell RNA sequencing of peripheral blood mononuclear cells from migraine patients and controls.
resultsEP300, SIRT1, and SLC16A1 were identified as key regulators of migraine susceptibility across methylation, expression, and protein levels. EP300 and SLC16A1 were associated with increased migraine risk, while SIRT1 conferred a protective effect. Mediation analyses revealed that genetic effects of these genes were partially transmitted through specific immune cell subsets, particularly B cells and natural killer T cells. Single-cell transcriptomic profiling further demonstrated EP300 upregulation in B cells and T cells of migraine patients. These findings support a novel “lactylation–immune mediation–migraine axis” linking metabolic and immune dysregulation to migraine pathogenesis.
conclusionThis integrative multi-omics analysis uncovers lactylation-related genes as causal drivers of migraine through immunometabolic pathways. Targeting lactylation-regulated metabolic and immune mechanisms may offer novel precision therapeutic strategies for migraine, particularly in patients with inflammatory or metabolic endophenotypes.
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