ReviewThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology2025
Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis.
Review in The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed.
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Reframing Alzheimer's Disease Through a Redox-Metabolic Framework.International journal of molecular sciences · 2026Review
- Lactate as a metabolic-epigenetic hub in neurological disorders.Metabolic brain disease · 2026Review
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- Review
- Low Dose Ketamine Preconditions Astrocyte Mitochondria to Achieve Antidepressant Efficacy via Adenosine, Humanin, and Melatonin Upregulation and Efflux.Alpha psychiatry · 2026Article
- Integration of Raman spectroscopy and chemometric modeling to study lactose effects on human glioblastoma brain cells.RSC advances · 2026Article
- Article
- Dysfunction of the CD38-Miro1 Axis Disrupts Astrocyte-neuron Mitochondrial Transfer in Alzheimer's Disease: Mechanisms and Therapeutic Restoration.Journal of molecular neuroscience : MN · 2026Review
- Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets.Molecular biomedicine · 2026Review
- Physical Exercise Counteracts Impaired Cognition by Improving Mitochondrial Function.International journal of molecular sciences · 2026Review
- Depletion of BIS in astrocytes aggravates reactive gliosis following photothrombotic brain injury.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Metabolic-Epigenetic-Immune axis in Ischemic Stroke: Lactate-derived Lactylation as a Key Regulator.Metabolic brain disease · 2026Review
- Altered astrocyte-neuron crosstalk in progressive supranuclear palsy: integrated evidence from proteomics and magnetic resonance spectroscopy.Acta neuropathologica · 2026Article
- Lactate and lactylation in neuropsychiatric disorders: a comprehensive review.Molecular biology reports · 2026Review
- LRRK2 I1371V Mutation Drives Astrocytic Glucose Metabolism Failure and Induces Integrated ER-Mitochondria-Lysosome Dysfunction in Parkinson's Disease.International journal of molecular sciences · 2026Article
- Glial cell and perineuronal net interactions in the dorsal striatum of aged mice.bioRxiv : the preprint server for biology · 2026Article
- LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
- Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications.Biomedicines · 2026Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The brain's substantial metabolic requirements, consuming a substantial fraction of the body's total energy despite its relatively small mass, necessitate sophisticated metabolic mechanisms for efficient energy distribution and utilization. The astrocyte-neuron lactate shuttle (ANLS) hypothesis has emerged as a fundamental framework explaining the metabolic cooperation between astrocytes and neurons, whereby astrocyte-derived lactate serves as a crucial energy substrate for neurons. This review synthesizes current understanding of brain energy metabolism, focusing on the dual roles of lactate as both an energy substrate and a signaling molecule. We examine the molecular underpinnings of metabolic compartmentalization, particularly the differential expression of lactate dehydrogenase (LDH) isozymes between astrocytes and neurons, which facilitates directional lactate flux. Recent evidence has challenged aspects of the classical ANLS model, revealing greater metabolic flexibility in neurons than previously recognized, including substantial LDHA expression and direct glucose utilization capabilities. Our recent studies on LDHB-deficient neurons provide new insights into the compensatory mechanisms and limitations of neuronal lactate metabolism, suggesting a more nuanced understanding of the ANLS hypothesis. Furthermore, we discuss lactate's emerging role as a signaling molecule in synaptic plasticity, memory formation, and neuroprotection, particularly in ischemic conditions where elevated lactate levels correlate with enhanced neuronal survival through prostaglandin E2-mediated vasodilation. This comprehensive review integrates classical perspectives with recent advances, providing an updated framework for understanding brain lactate metabolism and its therapeutic implications in neurological disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.