ArticlePloS one2022
Physiology of PNS axons relies on glycolytic metabolism in myelinating Schwann cells.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Biohybrid cochlear implants: neural interfaces, regenerative pathways, and translational benchmarks.Journal of neuroengineering and rehabilitation · 2026Review
- Bioenergetic failure in diabetic peripheral neuropathy: from glucotoxicity to multidimensional metabolic imbalance.Journal of neurology · 2026Review
- Aging and Peripheral Nerve Injuries: Impaired Repair, Inflammaging Impact, and Regeneration Resistance.Biomedicines · 2026Review
- Prostaglandin D2 Synthase Controls Schwann Cells Metabolism and Peripheral Myelin Homeostasis.Glia · 2026Article
- Diabetic neuropathy's immune-metabolic network: mechanistic complexity, therapeutic challenges, and the path forward.Frontiers in immunology · 2026Review
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- PMP2 Enhances Schwann Cell Metabolism and Promotes Myelination.Journal of neurochemistry · 2025Article
- Histone and non-histone lactylation: molecular mechanisms, biological functions, diseases, and therapeutic targets.Molecular biomedicine · 2025Review
- Molecular and cellular mechanisms underlying peripheral nerve injury-induced cellular ecological shifts: Implications for neuroregeneration.IBRO neuroscience reports · 2025Review
- Pmp2+ Schwann Cells Maintain the Survival of Large-Caliber Motor Axons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Unveiling the Role of Schwann Cell Plasticity in the Pathogenesis of Diabetic Peripheral Neuropathy.International journal of molecular sciences · 2024Review
- Oligodendrocytes: Myelination, Plasticity, and Axonal Support.Cold Spring Harbor perspectives in biology · 2024Review
- Schwann Cell Development and Myelination.Cold Spring Harbor perspectives in biology · 2024Review
- The Role of PKM2 in Multiple Signaling Pathways Related to Neurological Diseases.Molecular neurobiology · 2024Review
- Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts.Pharmaceuticals (Basel, Switzerland) · 2024Review
- New perspectives in diabetic neuropathy.Neuron · 2023Review
- Functional attachment of primary neurons and glia on radiopaque implantable biomaterials for nerve repair.Nanomedicine : nanotechnology, biology, and medicine · 2023Article
- Important Cells and Factors from Tumor Microenvironment Participated in Perineural Invasion.Cancers · 2023Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While lactate shuttle theory states that glial cells metabolize glucose into lactate to shuttle it to neurons, how glial cells support axonal metabolism and function remains unclear. Lactate production is a common occurrence following anaerobic glycolysis in muscles. However, several other cell types, including some stem cells, activated macrophages and tumor cells, can produce lactate in presence of oxygen and cellular respiration, using Pyruvate Kinase 2 (PKM2) to divert pyruvate to lactate dehydrogenase. We show here that PKM2 is also upregulated in myelinating Schwann cells (mSC) of mature mouse sciatic nerve versus postnatal immature nerve. Deletion of this isoform in PLP-expressing cells in mice leads to a deficit of lactate in mSC and in peripheral nerves. While the structure of myelin sheath was preserved, mutant mice developed a peripheral neuropathy. Peripheral nerve axons of mutant mice failed to maintain lactate homeostasis upon activity, resulting in an impaired production of mitochondrial ATP. Action potential propagation was not altered but axonal mitochondria transport was slowed down, muscle axon terminals retracted and motor neurons displayed cellular stress. Additional reduction of lactate availability through dichloroacetate treatment, which diverts pyruvate to mitochondrial oxidative phosphorylation, further aggravated motor dysfunction in mutant mice. Thus, lactate production through PKM2 enzyme and aerobic glycolysis is essential in mSC for the long-term maintenance of peripheral nerve axon physiology and function.
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Registered trials
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 OpenQuestion graph.