Abstract: Lactate, a byproduct of glycolysis, was thought to be a metabolic waste until the discovery of the Warburg effect. Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions. The Astrocyte-Neuron Lactate Shuttle has clarified that lactate plays a pivotal role in the central nervous system. Moreover, protein lactylation highlights the novel role of lactate in regulating transcription, cellular functions, and disease development. This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases, thus providing optimal perspectives for future research.

Key words: Alzheimer’s disease, Astrocyte-Neuron Lactate Shuttle, brain, central nervous system, glucose metabolism, glycolysis, neuroinflammation, Parkinson’s disease, protein lactylation, signaling molecule