Pharmacological stabilization of hypoxia-inducible factor 1-α dampens the interferon response and promotes glycolysis in Aicardi-Goutières syndrome - PubMed
2 hours ago
- #interferon response
- #HIF-1α
- #Aicardi-Goutières syndrome
- Aicardi-Goutières syndrome (AGS) is a genetic type I interferon (IFN)-mediated disease with neurological onset in utero or childhood.
- Single-cell transcriptomics and metabolomics reveal a loss of HIF-1α expression and activity in AGS patients, leading to a metabolic switch favoring oxidative phosphorylation over glycolysis.
- Mitochondrial stress and accumulation of cytosolic double-stranded DNA/RNA were observed in AGS patients.
- Pharmacological stabilization of HIF-1α reversed the metabolic switch, reduced mitochondrial stress, and dampened the IFN response.
- Targeting the HIF-1α pathway may offer a therapeutic approach for AGS.