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Lookup NU author(s): Dr Peter Massey, Professor Mark Cunningham
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2024 GSK. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd. One third of epilepsy patients are resistant to treatment with current anti-seizure medications. The ketogenic diet is used to treat some forms of refractory epilepsy, but the mechanism of its action has not yet been elucidated. In this study, we aimed to investigate whether the hydroxycarboxylic acid receptor 2 (HCA2), a known immunomodulatory receptor, plays a role in mediating the protective effect of this diet. We demonstrate for the first time that selective agonists at this receptor can directly reduce seizures in animal models. Agonists also reduce network activity in rodent and human brain slices. Ketogenic diet is known to increase circulating levels of endogenous HCA2 agonists, and we show that the effect of ketogenic diet in reducing seizures in the 6 Hz seizure model is negated in HCA2-deficient mice. Our data support the potential of HCA2 as a target for the treatment of epilepsy and potentially for neurodegenerative diseases.
Author(s): Richardson JC, Higgins GA, Upton N, Massey P, Cunningham M, Wilson S, Holenz J, Taylor C, Lavrov A, Lin H, Matsuoka Y, Brown AJ
Publication type: Article
Publication status: Published
Journal: Pharmacology Research and Perspectives
Year: 2024
Volume: 12
Issue: 6
Print publication date: 01/12/2024
Online publication date: 22/10/2024
Acceptance date: 24/09/2024
Date deposited: 06/11/2024
ISSN (electronic): 2052-1707
Publisher: John Wiley and Sons Ltd
URL: https://doi.org/10.1002/prp2.70026
DOI: 10.1002/prp2.70026
Data Access Statement: Data available on request due to privacy/ethical restrictions.
PubMed id: 39439218
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