{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T10:38:14Z","timestamp":1793270294600,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Seizures can cause progressive neuronal damage. Our previous studies found that RAF1 mediates vitamin D's alleviation of seizures, but the mechanism by which RAF1 acts in seizures remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The pilocarpine\u2010induced acute seizure\u2010associated neuronal injury (Pilo\u2010ASNI) model and glutamate\u2010treated HT22 cells were used. Behavioral assessments were performed to evaluate seizure severity and latency; histopathological staining was performed to examine neuronal damage and survival; and cellular assays were performed to assess cell viability, cytotoxicity, and DNA damage. Transcriptome sequencing, Co\u2010immunoprecipitation, molecular docking, ChIP\u2010qPCR, and ferroptosis indicators were employed to elucidate the molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RAF1 expression was markedly upregulated in the Pilo\u2010ASNI model and glutamate\u2010treated HT22 cells. RAF1 knockdown attenuated seizure severity and neuronal damage. Mechanistic studies in HT22 cells revealed that RAF1 inhibited Gstt1 transcription and promoted ferroptosis by promoting KDM1A recruitment and reducing H3K4me2 levels in the promoter region of Gstt1. Disrupting the RAF1\u2010KDM1A interaction could inhibit ferroptosis and alleviate nerve damage, whereas Gstt1 knockdown reverses the protective effect of RAF1 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study revealed a RAF1\u2010driven pathway involving KDM1A\u2010mediated epigenetic suppression of Gstt1 and subsequent ferroptosis, which may represent a potential target for neuroprotective intervention in seizures.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71177","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T10:00:24Z","timestamp":1791626424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>RAF1<\/scp>\n                    Promotes Gstt1\u2010Mediated Ferroptosis by Promoting\n                    <scp>KDM1A<\/scp>\n                    Recruitment to Facilitate Pilocarpine\u2010Induced Acute Seizure\u2010Associated Neuronal Injury"],"prefix":"10.1002","volume":"32","author":[{"given":"Tiantian","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Neonatology Haikou Maternal and Child Health Hospital  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neonatology Haikou Maternal and Child Health Hospital  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Hainan University  Haikou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Haikou Maternal and Child Health Hospital  Haikou 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