DIRAS2 modulates MAPK pathway-mediated ferroptosis to regulate excitation/inhibition balance and seizure susceptibility - PubMed
4 hours ago
- #ferroptosis
- #epilepsy
- #DIRAS2
- DIRAS2, a Ras-related GTPase, modulates the MAPK pathway to regulate ferroptosis and neuronal excitation/inhibition (E/I) balance.
- DIRAS2 is downregulated during epileptogenesis but upregulated in chronic epilepsy phases in both mouse models and human temporal lobe epilepsy patients.
- Overexpression of DIRAS2 reduces seizure susceptibility and neuronal hyperexcitability, while its knockdown exacerbates these conditions.
- DIRAS2 influences ferroptosis; its knockdown increases ferroptosis, whereas overexpression protects against it, with ferroptosis inhibitor Ferrostatin-1 reversing DIRAS2 knockdown effects.
- DIRAS2 regulates ferroptosis by inhibiting the ERK/p38 MAPK pathway, suggesting a potential therapeutic target for epilepsy.