{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:18:40Z","timestamp":1789121920534,"version":"build-2803163510"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NAWA\u2014the Polish National Agency for Academic Exchange","award":["PPI\/STE\/2020\/1\/00014\/DEC\/02"],"award-info":[{"award-number":["PPI\/STE\/2020\/1\/00014\/DEC\/02"]}]},{"award":["PPI\/STE\/2020\/1\/00014\/DEC\/02"],"award-info":[{"award-number":["PPI\/STE\/2020\/1\/00014\/DEC\/02"]}],"id":[{"id":"https:\/\/ror.org\/02jf81j23","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Seizures in several epilepsy syndromes cluster within narrow windows of the sleep\u2013wake cycle, even though the underlying molecular defects are present continuously. This narrative review asks how constitutive molecular pathologies give rise to state-dependent seizures. We integrated epilepsy genetics with sleep neurophysiology, drawing on literature retrieved from PubMed\/MEDLINE across eleven concept blocks, and organized the evidence around four gene families: nicotinic acetylcholine receptor subunits, KCNT1, the GATOR1\u2013mTOR complex, and thalamocortical calcium and HCN channels. Across these pathways, the genetic evidence ranges from well-established monogenic causation to susceptibility alleles of insufficient effect. We propose, as an integrative working model, that non-rapid eye movement (NREM) sleep converts continuous defects into state-bound seizures by strengthening thalamocortical coupling, withdrawing cholinergic tone and destabilizing arousal, with circadian phase adding a further layer of temporal control. In this model, sleep-state dependence may reflect the interaction between molecular lesions and vigilance states rather than the properties of any single gene. The strength of evidence for this link varies across gene families and is weakest for the GATOR1 pathway; much of the supporting evidence derives from animal, expression, and computational studies, whose extension to human syndromes remains inferential.<\/jats:p>","DOI":"10.3390\/cimb48090931","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:17:42Z","timestamp":1789114662000},"page":"931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanisms of Seizure Gating in Sleep-Related Epilepsy: Genes, Channels, Sleep Stages and Circadian Rhythm"],"prefix":"10.3390","volume":"48","author":[{"given":"Ozgun","family":"Yetkin","sequence":"first","affiliation":[{"name":"Polysomnography and Sleep Research Unit, Department of Developmental Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Baykan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurophysiology, EMAR Medical Center, 34367 Istanbul, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9800-9446","authenticated-orcid":false,"given":"Marcin","family":"Zarowski","sequence":"additional","affiliation":[{"name":"Polysomnography and Sleep Research Unit, Department of Developmental Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","unstructured":"Gowers, W.R. 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