期刊
JOURNAL OF INFLAMMATION RESEARCH
卷 14, 期 -, 页码 3367-3392出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/JIR.S287740
关键词
epilepsy; inflammation; purinergic signaling; ATP; P2 receptors; P2X(7) receptor; P2Y(1) receptor; disease modification; drug refractoriness
类别
资金
- Science Foundation Ireland [17/CDA/4708, 16/RC/3948]
- European Regional Development Fund
- FutureNeuro
- Irish Research Council (Government of Ireland Postdoctoral Fellowship Programme) [GOIPD/2020/865]
The treatment of epilepsy remains challenging, with chronic inflammation playing a crucial role in its pathogenesis. Identifying and targeting mechanisms that regulate inflammation may be a promising strategy for future epilepsy treatment. ATP-gated receptors are considered novel drug targets for epilepsy, showing potential for anticonvulsant and antiepileptic effects.
Treatment of epilepsy remains a clinical challenge, with >30% of patients not responding to current antiseizure drugs (ASDs). Moreover, currently available ASDs are merely symptomatic without altering significantly the progression of the disease. Inflammation is increasingly recognized as playing an important role during the generation of hyperexcitable networks in the brain. Accordingly, the suppression of chronic inflammation has been suggested as a promising therapeutic strategy to prevent epileptogenesis and to treat drug-refractory epilepsy. As a consequence, a strong focus of ongoing research is identification of the mechanisms that contribute to sustained inflammation in the brain during epilepsy and whether these can be targeted. ATP is released in response to several pathological stimuli, including increased neuronal activity within the central nervous system, where it functions as a neuro- and gliotransmitter. Once released, ATP activates purinergic P2 receptors, which are divided into metabotropic P2Y and ionotropic P2X receptors, driving inflammatory processes. Evidence from experimental models and patients demonstrates widespread expression changes of both P2Y and P2X receptors during epilepsy, and critically, drugs targeting both receptor subtypes, in particular the P2Y(1) and P2X(7) subtypes, have been shown to possess both anticonvulsive and antiepileptic potential. This review provides a detailed summary of the current evidence suggesting ATP-gated receptors as novel drug targets for epilepsy and discusses how P2 receptor-driven inflammation may contribute to the generation of seizures and the development of epilepsy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据