Abstract Ischemic cerebrovascular disease involves complex interactions between metabolic reprogramming and epigenetic regulation. Recent studies indicate that enhanced glycolysis and lactate accumulation under hypoxic conditions not only maintain cell viability by supplying energy but also participate in disease regulation through lactylation. Lactylation regulates gene expression, immune polarization, metabolic enzyme activity, and angiogenesis through epigenetic remodeling. In ischemic cerebrovascular disease, lactylation exerts dual roles: on one hand, it can induce neuronal death, exacerbate neuroinflammation, and form a vicious metabolic cycle; on the other hand, it can influence immune cell function and gene expression, thereby exerting neuroprotective effects. Accordingly, targeting lactate metabolism or lactylation-modifying enzymes holds considerable therapeutic potential. Nevertheless, the spatiotemporal regulation, synergistic effects, and broader physiopathological implications of lactylation warrant further in-depth investigation. This review systematically summarizes the role of the “glycolysis-lactate-lactylation” axis in the pathogenesis of ischemic cerebrovascular disease, and discusses its potential as a therapeutic target.
Xie et al. (2026) studied this question.