ArticleFrontiers in immunology2025
RORα-activated mitophagy attenuating hypoxic-ischemic encephalopathy via suppression of microglial cGAS-STING axis.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Glycerol-3-Phosphate Attenuates Hypoxic-Ischemic Brain Injury via Modulation of Microglia-Mediated Neuroinflammation.Neurochemical research · 2026Article
- Mitochondrial dysfunction in neonatal brain injury: from molecular mechanisms to therapeutic interventions.Journal of translational medicine · 2026Review
- Inhibition of Microglial TRPV1 Ameliorates Brain Injury After Intracerebral Hemorrhage by Suppressing AMPK/PINK1-Mediated Mitophagy.CNS neuroscience & therapeutics · 2026Article
- Cerebral Ischemia-Reperfusion Injury: Unraveling the Mitophagy-Oxidative Stress Axis for Neuroprotective Strategies.International journal of molecular sciences · 2026Review
- (+)-JQ1 Upregulates SIRT3 to Suppress cGAS/STING Pathway-Mediated Neuronal Inflammation and Ferroptosis After Hypoxic-Ischemic Encephalopathy.Drug design, development and therapy · 2026Article
- RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Hypoxic-ischemic encephalopathy (HIE) involves neuroinflammation driven by microglial activation, yet regulatory mechanisms remain poorly defined. This study investigates how Retinoic Acid Receptor-Related Orphan Receptor Alpha (RORα) modulates mitophagy to suppress mtDNA-cGAS-STING-NLRP3 signaling in aging microglia, offering therapeutic potential for HIE. Methods: A multi-omics approach combining single-cell RNA sequencing (scRNA-seq) of an HIE rat model, Weighted Gene Co-Expression Network Analysis (WGCNA), and LASSO regression identified RORα as a pivotal regulator. Results: Multi-omics integration revealed RORα as a hub gene linked to inflammatory and metabolic pathways. RORα activation enhanced mitophagy, reducing mtDNA leakage by 43% and cGAS-STING activity by 68%, which suppressed NLRP3 inflammasome activation ( Conclusion: RORα alleviates HIE by resolving microglial neuroinflammation through mitophagic inhibition of mtDNA-cGAS-STING-NLRP3 signaling. These findings position RORα as a novel therapeutic target for HIE, bridging mitochondrial quality control and neuroimmunology.
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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 Socratic graph.