Research progress on histone lactylation modification in ischemic stroke: mechanisms and therapeutic potential.

Abstract

Ischemic stroke (IS) is a leading cause of death and disability worldwide, with a complex pathogenesis involving neuroinflammation, oxidative stress, and disruption of the blood-brain barrier. Recent research has brought histone lactylation into focus as a novel epigenetic modification that plays a crucial role in IS. Under cerebral ischemia and hypoxia, lactate levels rise, providing an alternative energy source to support ischemic brain regions. Lactate also functions as a signaling molecule, regulating key processes such as neuroprotection, angiogenesis, and anti-inflammatory responses. This review synthesizes the current research on histone lactylation in IS, emphasizing its role in neuronal survival, inflammatory regulation, and blood-brain barrier integrity. A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science, focusing on studies published from 2015 to 2023. Additionally, the review explores the potential of histone lactylation as a therapeutic target for post-stroke recovery. Histone lactylation can be targeted therapeutically through the use of specific inhibitors or enhancers of acetyltransferase and deacetylase enzymes, offering a promising strategy for modulating stroke-related cellular processes. By integrating recent findings, this review aims to provide new insights into ischemic stroke and promote the development of innovative therapeutic strategies.