Lactate lactylation in neural pathophysiology: Bridging metabolism and neurodegeneration

Lactate is the end product of anaerobic glycolysis. Its functions in the central nervous system have garnered increasing attention as new roles continue to emerge. Beyond serving as an energy source and a substrate for gluconeogenesis, lactate also functions as a signaling molecule that regulates diverse cellular activities. Recent studies have demonstrated that lactate contributes to protein lactylation-a novel posttranslational modification-and plays a crucial role in metabolic reprogramming. Additionally, lactate has been associated with neuroinflammation and multiple neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and others. This review summarizes the regulatory mechanisms of lactate metabolism and lactylation, along with findings related to lactate's involvement in the nervous system and neurodegenerative conditions. Specifically, it highlights the effects of lactate and lactylation on glial cells and neurons in the brain, and outlines how lactate levels and lactylation status influence disease progression in neurodegenerative disorders. The potential mechanisms by which lactylation contributes to neurodegenerative pathologies are also discussed. These insights may provide novel avenues for exploring the role of lactylation in neurological disease.