{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:47:02Z","timestamp":1781758022761,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T00:00:00Z","timestamp":1733270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004801","name":"Shota Rustaveli National Science Foundation","doi-asserted-by":"publisher","award":["YS\u201021\u2010347"],"award-info":[{"award-number":["YS\u201021\u2010347"]}],"id":[{"id":"10.13039\/501100004801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001862","name":"Svenska Forskningsr\u00e5det Formas","doi-asserted-by":"publisher","award":["2021\u201003209"],"award-info":[{"award-number":["2021\u201003209"]}],"id":[{"id":"10.13039\/501100001862","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Inositols play significant roles in biological systems. Myo\u2010inositol (MI), the most prevalent isomer, functions as an osmolyte and mediates cell signal transduction. Other notable isomers include Scyllo\u2010inositol (SCI) and D\u2010Chiro\u2010inositol (DCHI). Our previous investigations have highlighted MI's potential antiepileptogenic effects, although its exact mechanisms of action during epileptogenesis remain unclear. A critical, unexplored area is how inositols interact with proteins. Additionally, the antiepileptogenic capabilities of SCI and DCHI have yet to be determined. This study seeks to address these gaps.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inositol interacting proteins were identified by cellular thermal shift assay. Status epilepticus (SE) in rats was induced using kainic acid (KA), followed by a 28\u2010day treatment with either MI, SCI, DCHI, or saline. The duration and frequencies of behavioral spontaneous recurrent seizures (SRS) were scored for 8\u2009weeks by 24\u2009h video monitoring system. The effects of inositol treatment on spatial learning and memory deficits associated with epileptogenesis were evaluated by Morris water maze test. The changes in protein amounts were studied by Western immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified several proteins that interact with inositols, noting both commonalities and isomer\u2010specific associations. For the first time, we demonstrated that the treatment with SCI and DCHI, alongside MI, significantly reduces the frequency and duration of behavioral SRS in a KA\u2010induced post\u2010status epilepsy model in rats. This reduction persisted for 4\u2009weeks post\u2010treatment. Moreover, all three inositol isomers mitigated spatial learning and memory deficits associated with epileptogenesis. Alterations in the inositol interacting proteins: alpha synuclein and 14\u20103\u20103 theta were further examined 8\u2009weeks post\u2010SE in the hippocampus and neocortex of rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Myo\u2010inositol, SCI and DCHI interact with a number of proteins involved in different biological pathways. All studied inositol isomers express long\u2010term beneficial effects on KA\u2010induced SRS and the associated comorbidities. Inositols can be successfully used in the future for translational research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Epilepsy is a common neurological disorder characterized by spontaneous recurrent seizures and a range of associated comorbidities. The process that leads to the development of epilepsy is called epileptogenesis, and currently, no medication can effectively prevent it. Our study investigated the effects of a group of compounds\u2014myo\u2010inositol, scyllo\u2010inositol, and D\u2010chiro\u2010inositol\u2014that have potential antiepileptogenic properties on epilepsy induced by kainic acid. We found that: (i) the three inositol isomers share some common target proteins and also have unique ones and (ii) all of them counteract epileptogenesis and the related cognitive impairments.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.13061","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T06:24:29Z","timestamp":1733379869000},"page":"120-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Preventing epileptogenesis by interaction between inositol isomers and proteins"],"prefix":"10.1002","volume":"10","author":[{"given":"Lia","family":"Tsverava","sequence":"first","affiliation":[{"name":"Institute of Chemical Biology Ilia State University  Tbilisi Georgia"},{"name":"Iv. 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