REVIEW article
Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Lactate and Cognition: A Dual Modulator
Wen Yang 1,2
Yu Xu 2
Kunhua Wang 1
1. Yunnan University, Kunming, China
2. First Affiliated Hospital of Kunming Medical University, Kunming, China
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Abstract
Lactate, traditionally regarded as a byproduct of glycolysis, has emerged as a key metabolic substrate and signaling molecule in the brain. Through the astrocyte–neuron lactate shuttle, lactate provides an essential link between energy metabolism and neuronal function. Beyond its metabolic role, lactate influences synaptic plasticity, neuroinflammation, mitochondrial dynamics, and epigenetic regulation, thereby exerting multifaceted effects on cognitive processes. Accumulating evidence demonstrates that lactate acts as a double-edged regulator: under certain conditions, it promotes neuronal resilience and cognitive enhancement, whereas excessive accumulation or impaired transport may contribute to dysfunction. This review synthesizes current knowledge of lactate metabolism in the central nervous system, highlighting its physiological functions, bidirectional impact on cognition, and emerging role as both a biomarker and therapeutic target. A deeper understanding of lactate-mediated mechanisms may pave the way for novel strategies in the prevention and intervention of cognitive impairment. Clinically, lactate is best interpreted as a context-sensitive metabolic readout rather than a standalone disease-specific biomarker.
Summary
Keywords
Astrocyte–neuron lactate shuttle, Cognition, Epigenetic regulation, Lactate, Neuroinflammation, synaptic plasticity
Received
13 November 2025
Accepted
11 February 2026
Copyright
© 2026 Yang, Xu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Wen Yang
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