Role of Histone Lactylation in Neurological Disorders

Lactate is not only the end product of glycolysis but also plays a key role in epigenetic regulation. Recently, lactate-derived histone lactylation has been identified as a novel epigenetic modification that can directly influence gene transcription. Histone lactylation has been associated with various pathological conditions and shows significant therapeutic potential. However, studies on histone lactylation in central nervous system diseases are still quite limited. In this review, we summarize the latest research progress on histone lactylation, detailing the specific mechanisms and sites of histone lactylation, including lactylation and delactylation. We also discuss the role of histone lactylation in Alzheimer’s disease (glycolysis/H4K12la/PKM2 feedback loop), depression (neuronal excitation), neuroinflammation (anti-inflammatory/pro-inflammatory balance of microglia), aging, stroke (infarct volume), and glioblastoma (activation of oncogenes), pointing out the research directions for the future. This may provide new ideas for the diagnosis and treatment of neurological diseases.