Molecular regulation of brain metabolism underlying circadian epilepsy


Extensive study has demonstrated that epilepsy occurs with greater frequency at certain times in the 24-h cycle. Although these findings implicate an overlap between the circadian rhythm and epilepsy, the molecular and cellular mechanisms underlying this circadian regulation are poorly understood. Because the 24-h rhythm is generated by the circadian molecular system, it is not surprising that this system comprised of many circadian genes is implicated in epilepsy. We summarized evidence in the literature implicating various circadian genes such as Clock, Bmal1, Per1, Rev-erb⍺, and Ror⍺ in epilepsy. In various animal models of epilepsy, the circadian oscillation and the steady-state level of these genes are disrupted. The downstream pathway of these genes involves a large number of metabolic pathways associated with epilepsy. These pathways include pyridoxal metabolism, the mammalian target of rapamycin pathway, and the regulation of redox state. We propose that disruption of these metabolic pathways could mediate the circadian regulation of epilepsy. A greater understanding of the cellular and molecular mechanism of circadian regulation of epilepsy would enable us to precisely target the circadian disruption in epilepsy for a novel therapeutic approach.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Additional Information: © 2021 International League Against Epilepsy. This is the peer reviewed version of the following article: Chan, F, Liu, J. Molecular regulation of brain metabolism underlying circadian epilepsy. Epilepsia. 2021; 62(Suppl. 1): S32– S48, which has been published in final form at: This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
Uncontrolled Keywords: circadian,clock genes,epigenetic,Epilepsy,metabolism
Publication ISSN: 1528-1167
Last Modified: 15 May 2024 16:23
Date Deposited: 04 Nov 2022 16:48
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Related URLs: https://onlinel ... .1111/epi.16796 (Publisher URL)
PURE Output Type: Article
Published Date: 2021-02
Published Online Date: 2021-01-04
Accepted Date: 2020-12-01
Authors: Chan, Felix (ORCID Profile 0000-0002-4867-9636)
Liu, Judy

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