{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:13:17Z","timestamp":1773389597167,"version":"3.50.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Temporal lobe epilepsy (TLE) is a common neurological disorder frequently resistant to pharmacological treatment, yet its molecular mechanisms remain incompletely understood. Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is a post-transcriptional regulator implicated in neuronal stress responses; however, its role in epilepsy and redox-inflammatory signaling remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An integrative multi-omics strategy combining single-cell transcriptomics, bulk RNA sequencing, and bioinformatics analyses was employed, followed by validation in human epileptic hippocampal tissues, kainic acid (KA)- and pentylenetetrazol (PTZ)-induced mouse models, as well as\n                      <jats:italic>in vitro<\/jats:italic>\n                      glutamate-induced neuronal injury models. Mechanistic investigations were performed using adeno-associated virus (AAV)-mediated CPEB1 overexpression and knockdown, together with pharmacological modulation of the SIRT1 and NRF2 pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CPEB1 was markedly upregulated in neurons from both TLE patients and experimental models. Neuronal overexpression of CPEB1 increased seizure susceptibility, exacerbated neuronal loss, and promoted oxidative stress, proinflammatory cytokine release, and ferroptosis, whereas CPEB1 knockdown exerted robust neuroprotective effects. Mechanistically, CPEB1 suppressed SIRT1 activity, leading to enhanced acetylation-dependent destabilization of NRF2, impaired downstream SLC7A11\/GPX4 antioxidant signaling, and excessive reactive oxygen species (ROS) accumulation, ultimately triggering ferroptotic neuronal death. Importantly, pharmacological inhibition of SIRT1 or NRF2 abolished the neuroprotective effects of CPEB1 knockdown, confirming the critical role of the CPEB1\u2013SIRT1\u2013NRF2 acetylation axis in TLE pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CPEB1 aggravates neuronal injury in TLE by driving ferroptosis\u2013neuroinflammation crosstalk through suppression of the SIRT1\u2013NRF2 acetylation axis. Targeting this pathway may provide a promising therapeutic strategy for drug-resistant epilepsy and related neurodegenerative disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1727784","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:25:35Z","timestamp":1773379535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CPEB1 drives ferroptosis\u2013neuroinflammation crosstalk in temporal lobe epilepsy via the SIRT1\u2013NRF2 acetylation axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Cong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, Heilongjiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhipeng","family":"You","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, 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