ArticleCNS neuroscience & therapeutics2024
Hyperglycemia-induced Sirt3 downregulation increases microglial aerobic glycolysis and inflammation in diabetic neuropathic pain pathogenesis.
Article in CNS neuroscience & therapeutics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Targeted nanovesicular delivery of dexmedetomidine modulates microglial lysosomal function via Sirt3 signaling to ameliorate neurodegenerative pathology.Neural regeneration research · 2026Article
- Sedanolide alleviates LPS‑induced depressive‑like behaviors by modulating the C3a/C3aR signaling axis and microglial glycolysis.Molecular medicine reports · 2026Article
- Buwang Formula Regulates Microglial Metabolic Reprogramming and Modulates the mTOR/HIF-1α Pathway to Reduce Neuroinflammation in Diabetic Mice.Pharmaceuticals (Basel, Switzerland) · 2026Article
- From sugar to flames: the detrimental role of pyroptosis in diabetes-associated bone loss.Molecular biology reports · 2026Review
- PRMT6 inhibition or deficiency attenuates diabetic neuropathic pain in male mice and is associated with reduced spinal neuroinflammation, microgliosis, and altered p53-p21 signaling.Journal of neuroinflammation · 2026Article
- Dihydrosanguinarine: A Review of Its Pharmacology, Structure-Activity Relationship, Toxicity, Pharmacokinetics, and Clinical Prospects.International journal of molecular sciences · 2026Review
- Neuronal metabolism role in ketogenic diet improvements in bortezomib-induced painful peripheral neuropathy mouse model.Pain reports · 2026Article
- Metformin attenuates HSV-1-induced neuropathic pain by restoring Sirt3-mediated mitophagy.Cell communication and signaling : CCS · 2026Article
- Glial Triad in Diabetic Neuropathy: Central Players in Neuropathic Pain Pathogenesis and Disease-Modifying Therapeutic Avenues.Biomedicines · 2026Review
- BRG1 orchestrates diabetic corneal neuropathy via PI3K/AKT-mediated glycolytic reprogramming.Eye and vision (London, England) · 2026Article
- Hyperglycemia promotes SIRT3-mediated deacetylation of SARM1 to exacerbate diabetic peripheral neuropathy in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Astrocytic SIRT3 Alleviates Neuroinflammatory Responses After Cerebral Ischemia/reperfusion by Inhibiting the cGAS-STING Pathway.Inflammation · 2026Article
- From pathophysiology to therapy: molecular mechanisms of stem cell and extracellular vesicle-mediated repair in diabetic peripheral neuropathy.Frontiers in cell and developmental biology · 2026Review
- Metabolite-neuro-immune relay in chronic pain: spatial-temporal lactate, succinate and itaconate signalling as drivers of glial reprogramming and neuronal sensitisation.Frontiers in pharmacology · 2026Review
- The pivotal role of immunometabolism in diabetic neuropathy and its potential therapeutic strategies.Frontiers in endocrinology · 2026Review
- Sirtuins in mitophagy: key gatekeepers of mitochondrial quality.Molecular and cellular biochemistry · 2025Review
- Macrophage polarization in diabetic vascular complications: mechanistic insights and therapeutic targets.Journal of translational medicine · 2025Review
- Microglial metabolic reprogramming: Aucubin inhibits aldose reductase to reverse diabetic neuropathic pain.World journal of diabetes · 2025Article
- Aucubin mitigates the elevation of microglial aerobic glycolysis and inflammation in diabetic neuropathic painWorld journal of diabetes · 2025Article
- Irisin Regulates Microglia M1/M2 Polarization and Promotes Autophagy Through the Sirt3 Pathway to Alleviate POCD.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
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Authors and funding
15 authors.
Funding
Abstract
backgroundHyperglycemia-induced neuroinflammation significantly contributes to diabetic neuropathic pain (DNP), but the underlying mechanisms remain unclear.
objectiveTo investigate the role of Sirt3, a mitochondrial deacetylase, in hyperglycemia-induced neuroinflammation and DNP and to explore potential therapeutic interventions. METHOD AND
resultsHere, we found that Sirt3 was downregulated in spinal dorsal horn (SDH) of diabetic mice by RNA-sequencing, which was further confirmed at the mRNA and protein level. Sirt3 deficiency exacerbated hyperglycemia-induced neuroinflammation and DNP by enhancing microglial aerobic glycolysis in vivo and in vitro. Overexpression of Sirt3 in microglia alleviated inflammation by reducing aerobic glycolysis. Mechanistically, high-glucose stimulation activated Akt, which phosphorylates and inactivates FoxO1. The inactivation of FoxO1 diminished the transcription of Sirt3. Besides that, we also found that hyperglycemia induced Sirt3 degradation via the mitophagy-lysosomal pathway. Blocking Akt activation by GSK69093 or metformin rescued the degradation of Sirt3 protein and transcription inhibition of Sirt3 mRNA, which substantially diminished hyperglycemia-induced inflammation. Metformin in vivo treatment alleviated neuroinflammation and diabetic neuropathic pain by rescuing hyperglycemia-induced Sirt3 downregulation.
conclusionHyperglycemia induces metabolic reprogramming and inflammatory activation in microglia through the regulation of Sirt3 transcription and degradation. This novel mechanism identifies Sirt3 as a potential drug target for treating DNP.
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