Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms

Brain takes up approximately 20% of the total body oxygen and glucose consumption due to its relatively high energy demand. Glucose is one of the major sources to generate ATP, the process of which can be realized via glycolysis, oxidative phosphorylation, pentose phosphate pathways and others. Lactate serves as a hub molecule amid these metabolic pathways, as it may function as product of glycolysis, substrate of a variety of enzymes and signal molecule. Thus, the roles of lactate in central nervous system (CNS) diseases need to be comprehensively elucidated. Histone lactylation is a novel lactate-dependent epigenetic modification that plays an important role in immune regulation and maintaining homeostasis. However, there's still a lack of studies unveiling the functions of histone lactylation in the CNS. In this review, we first comprehensively reviewed the roles lactate plays in the CNS under both physiological and pathological conditions. Subsequently, we've further discussed the functions of histone lactylation in various neurological diseases. Furthermore, future perspectives regarding histone lactylation and its therapeutic potentials in stroke are also elucidated, which may possess potential clinical applications.