ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Cordycepin Modulates Microglial M2 Polarization Coupled with Mitochondrial Metabolic Reprogramming by Targeting HKII and PDK2.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
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- Ultrasound-Responsive Piezoelectric Fibrous Membrane Promotes Neurological Recovery After TBI by Modulating Microglial Polarization via Restoring Mitochondrial Dynamic Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AiScience · 2026Article
- A C-Nucleoside Analogue of Cordycepin With High Metabolic Stability and Potent Anti-Psoriatic Activity via Microneedle Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Review
- Kinsenoside Targets IDH1 to Restore Microglial Immune-Metabolic Homeostasis for Alzheimer's Disease Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cordycepin alleviates nicotine withdrawal-induced anxietyDrug and alcohol dependence reports · 2026Article
- Targeted biohybrid nanoplatform for spinal cord injury treatment: Restoring microglial mitophagy and alleviating oxidative stress.Materials today. Bio · 2026Article
- Ferroptosis and macrophage polarization: mechanisms, interplay, and implications for medical applications.Cell death discovery · 2026Review
- Phytochemical and Fungal Bioactive Compounds in the "Brain Health Triad": A Narrative Review on Neurostimulating, Neurotrophic, and Neuroprotective Synergy.International journal of molecular sciences · 2026Review
- Microglial polarization in retinal neovascularization: Friend or foe?Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Targeting Microglial CD49a Inhibits Neuroinflammation and Demonstrates Therapeutic Potential for Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unraveling Parkinson's disease: The mystery of mitochondria and the role of aging.Genes & diseases · 2026Review
- A Hierarchical Microglial-Targeting Nanoplatform for the Therapy of Parkinson's Disease by Modulating Mitochondrial Dysfunction.Pharmaceutics · 2026Article
- Microglia-Neuron Crosstalk: An Intimate Molecular Conversation in Neurodegeneration.International journal of molecular sciences · 2026Review
- FTO-dependent mInflammation · 2026Article
- S100A8 aggravates sepsis-associated encephalopathy by promoting PFKFB3-dependent glycolysis and microglial neuroinflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
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Authors and funding
21 authors.
Funding
Abstract
The microenvironment mediated by the microglia (MG) M1/M2 phenotypic switch plays a decisive role in the neuronal fate and cognitive function of Alzheimer's disease (AD). However, the impact of metabolic reprogramming on microglial polarization and its underlying mechanism remains elusive. This study reveals that cordycepin improved cognitive function and memory in APP/PS1 mice, as well as attenuated neuronal damage by triggering MG-M2 polarization and metabolic reprogramming characterized by increased OXPHOS and glycolysis, rather than directly protecting neurons. Simultaneously, cordycepin partially alleviates mitochondrial damage in microglia induced by inhibitors of OXPHOS and glycolysis, further promoting MG-M2 transformation and increasing neuronal survival. Through confirmation of cordycepin distribution in the microglial mitochondria via mitochondrial isolation followed by HPLC-MS/MS techniques, HKII and PDK2 are further identified as potential targets of cordycepin. By investigating the effects of HKII and PDK2 inhibitors, the mechanism through which cordycepin targeted HKII to elevate ECAR levels in the glycolysis pathway while targeting PDK2 to enhance OCR levels in PDH-mediated OXPHOS pathway, thereby inducing MG-M2 polarization, promoting neuronal survival and exerting an anti-AD role is elucidated.
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