Friend or foe: Lactate in neurodegenerative diseases

Lactate, a byproduct of glycolysis, was considered as a metabolic waste until identified by studies on the Warburg effect. Increasing evidence elucidates that lactate functions as energy fuel, signaling molecule, and donor for protein lactylation. Altered lactate utilization is a common metabolic feature of the onset and progression of neurodegenerative diseases, such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Huntington's disease. This review offers an overview of lactate metabolism from the perspective of production, transportation and clearance, and the role of lactate in neurodegenerative progression, as well as a summary of protein lactylation and the signaling function of lactate in neurodegenerative diseases. Besides, this review delves into the dual roles of changed lactate metabolism during neurodegeneration and explores prospective therapeutic methods targeting lactate. We propose that elucidating the correlation between lactate and neurodegeneration is pivotal for exploring innovative therapeutic interventions for neurodegenerative diseases. •Altered lactate metabolism disorder is a common feature of the onset and progression of neurodegenerative diseases.•This review explores lactate metabolism, focusing on production, transport and clearance, and its role in neurodegeneration.•This review summarizes protein lactylation and the signaling function of lactate in neurodegenerative diseases.•This review delves into the dual role of lactate in neurodegeneration, exploring whether it serves as a friend or a foe.