DIRAS2 modulates MAPK pathway-mediated ferroptosis to regulate excitation/inhibition balance and seizure susceptibility

• 成果类型: Article
• 署名作者: Zhang, Chenlu; Hu, Liqin; Zhang, Hui; Yang, Min; Zhang, Yuansong; Zhang, Ningning; Xu, Yuanhang; Zhao, Yuping; Ren, Lingxin; Guo, Haokun; Li, Wei; Wang, Xuefeng; Yang, Yong; Tian, Xin
• 署名单位: Shanxi Medical University; Chongqing Medical University; Chongqing Medical University; Chongqing Medical University; Chongqing Medical University; Hunan University; Lanzhou University; Lanzhou University; North Sichuan Medical University; Qingdao University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2516011123
• 发表日期: 2026-03-31
• 页码: 2516011123
• 关键词: epilepsy; DIRAS2; ferroptosis; excitation and inhibition balance; MAPK; epilepsy

摘要

Epilepsy is a common neurological disorder that is widely believed to be associated with GTPase, has not been well understood regarding its role and function within the nervous system. In this study, we found that DIRAS2 is downregulated in the hippocampus during the epileptogenesis phase in a kainic acid- induced epilepsy model, while it is upregulated during the chronic phase in this epilepsy model and in patients with tibility and activity, whereas knockdown of DIRAS2 has an opposite effect. Whole- cell ferroptosis is involved in mediating the effects of DIRAS2. Knockdown of DIRAS2 can exacerbate ferroptosis, while overexpression protects against ferroptosis in both found that DIRAS2 regulates ferroptosis by inhibiting the extracellular signal- regulated for epilepsy treatment.