{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:28:42Z","timestamp":1793316522830,"version":"4.5.0"},"reference-count":175,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Lactate, traditionally regarded as a metabolic byproduct of glycolysis, is now recognized as a critical signaling molecule in the central nervous system. Emerging evidence indicates that lactate participates in a dynamic metabolic\u2013epigenetic regulatory network through protein lactylation, a post-translational modification capable of modulating chromatin structure and gene transcription. We summarize the physiological roles of lactate in neuronal\u2013glial metabolic coupling and highlight cell-type-specific functions of the lactate\u2013lactylation axis under both normal and pathological conditions. Particular emphasis is placed on its involvement in ischemic stroke, neurodegenerative diseases such as Alzheimer\u2019s disease and Parkinson\u2019s disease. Available findings indicate that this axis is integral to synaptic plasticity, neuroinflammatory balance, and metabolic homeostasis. Under pathological conditions, excessive lactate accumulation promotes aberrant lactylation patterns that may drive persistent inflammation, metabolic reprogramming, and neuronal dysfunction by reshaping chromatin accessibility and transcriptional landscapes. Collectively, the lactate\u2013lactylation axis represents a unifying mechanistic framework linking metabolic flux to epigenetic regulation in neurological disorders and may serve as a promising source of diagnostic biomarkers and precision therapeutic targets.<\/jats:p>","DOI":"10.3389\/fnmol.2026.1779468","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:31:53Z","timestamp":1775626313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["From metabolic substrate to epigenetic regulation: roles and mechanisms of lactylation in brain health and disease"],"prefix":"10.3389","volume":"19","author":[{"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"College of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruobing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]},{"name":"Rehabilitation Department, Heilongjiang Provincial Hospital of Traditional Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lei","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xicheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]},{"name":"Rehabilitation Department II, First Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1002\/ajmg.b.32691","article-title":"Aberrant transcriptomes and DNA methylomes define pathways that drive pathogenesis and loss of brain laterality\/asymmetry in schizophrenia and bipolar disorder","volume":"180","author":"Abdolmaleky","year":"2019","journal-title":"Am. 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