mtDNA leakage promotes neuron-glia crosstalk to induce epilepsy by cGAS-STING-driven neuroinflammation and serine metabolic reprogramming - PubMed
4 hours ago
- #epilepsy
- #neuroinflammation
- #metabolic-reprogramming
- Epilepsy involves metabolic dysregulation beyond neural hyperexcitability.
- Brain-specific deletion of Mic19 impairs mitochondrial integrity in neurons, leading to mtDNA leakage.
- Leaked mtDNA triggers cGAS-STING-dependent inflammatory signaling in microglia.
- Neuroinflammation causes sustained activation and metabolic reprogramming in astrocytes.
- Astrocytes upregulate glycolysis and enhance L-serine biosynthesis, which is converted to D-serine in neurons.
- D-serine acts as an NMDA receptor coagonist, enhancing neuronal excitability and exacerbating epilepsy.
- Pharmacologic inhibition of STING with H-151 suppresses seizures, suggesting a therapeutic strategy.