Yi Xie1,2,3 · Mengmeng Dai1,2,3 · Rui Liu1,2,3 · Ying Li1,2,3 · Hao Yan1,2,3 · Jiacheng Li1,2,3 · Xuantong Liu1,2,3 · Zhiyuan Yu1,2,3 · Shabei Xu1,2,3 · Wei Wang1,2,3,4 · Xiang Luo1,2,3

1 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 

2 Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China 

3 Hubei Stroke Clinical Research Center, Wuhan 430030, China 

4 Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

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.

Keywords

Ischemic cerebrovascular disease; Glycolysis; Lactate; Lactylation; Metabolic reprogramming; Neuroinflammation

[SpringerLink]