Zhang Yu-Mo, Yang Fei, Li Qian, Zhang Jian-Nan
School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
Int J Mol Sci. 2025 Aug 18;26(16):7949. doi: 10.3390/ijms26167949.
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.
乳酸不仅是糖酵解的终产物，还在表观遗传调控中发挥关键作用。最近，乳酸衍生的组蛋白乳酰化已被鉴定为一种新型表观遗传修饰，可直接影响基因转录。组蛋白乳酰化与多种病理状况相关，并显示出显著的治疗潜力。然而，关于中枢神经系统疾病中组蛋白乳酰化的研究仍然相当有限。在这篇综述中，我们总结了组蛋白乳酰化的最新研究进展，详细阐述了组蛋白乳酰化的具体机制和位点，包括乳酰化和去乳酰化。我们还讨论了组蛋白乳酰化在阿尔茨海默病（糖酵解/H4K12la/PKM2反馈回路）、抑郁症（神经元兴奋）、神经炎症（小胶质细胞的抗炎/促炎平衡）、衰老、中风（梗死体积）和胶质母细胞瘤（癌基因激活）中的作用，指出了未来的研究方向。这可能为神经疾病的诊断和治疗提供新思路。
