From lactate to lactylation: potential targets for the treatment of neurodegenerative diseases

Traditionally, lactate is regarded as a byproduct of anaerobic metabolism. With the deepening of related research, the roles of lactate in cellular energy metabolism, signal transduction, and microenvironment regulation have attracted increasing attention. Against this research background, the discovery of a novel post-translational modification - lactylation modification - has further expanded its biological functions. In the context of the increasingly aging global population, neurodegenerative diseases (ND) have become a significant challenge threatening global public health. Studies have reported that lactate metabolic disorders are common metabolic characteristics in the occurrence and development of ND. In summary, this article focuses on reviewing lactate and lactylation in the brain and their roles in ND. It comprehensively outlines the process from lactate to lactylation, highlights the close connection between brain lactate metabolism and ND, and explores potential molecular mechanisms underlying disease development - providing new perspectives for understanding ND pathogenesis. Additionally, this review systematically summarizes potential therapeutic strategies for ND based on regulating lactate metabolism, aiming to offer innovative approaches for disease prevention, diagnosis, and treatment.