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癫痫中的P2X7受体;在病理生理学中的作用及癫痫控制的潜在靶点

P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control.

作者信息

Engel Tobias, Jimenez-Pacheco Alba, Miras-Portugal Maria Teresa, Diaz-Hernandez Miguel, Henshall David C

机构信息

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland Dublin, Ireland ; Centre for the Study of Neurological Disorders, Royal College of Surgeons in Ireland Dublin, Ireland.

出版信息

Int J Physiol Pathophysiol Pharmacol. 2012;4(4):174-87. Epub 2012 Dec 26.

Abstract

The P2X7 receptor is an ATP-gated non-selective cation-permeable ionotropic receptor selectively expressed in neurons and glia in the brain. Activation of the P2X7 receptor has been found to modulate neuronal excitability in the hippocampus and it has also been linked to microglia activation and neuroinflammatory responses. Accordingly, interest developed on the P2X7 receptor in disorders of the nervous system, including epilepsy. Studies show that expression of the P2X7 receptor is elevated in damaged regions of the brain after prolonged seizures (status epilepticus) in both neurons and glia. P2X7 receptor expression is also increased in the hippocampus in experimental epilepsy. Recent data show that mice lacking the P2X7 receptor display altered susceptibility to status epilepticus and that drugs targeting the P2X7 receptor have potent anticonvulsant effects. Together, this suggests that P2X7 receptor ligands may be useful adjunctive treatments for refractory status epilepticus or perhaps pharmacoresistant epilepsy. This review summarizes the evidence of P2X7 receptor involvement in the pathophysiology of epilepsy and the potential of drugs targeting this receptor for seizure control.

摘要

P2X7受体是一种ATP门控的非选择性阳离子通透型离子otropic受体,在大脑中的神经元和胶质细胞中选择性表达。已发现P2X7受体的激活可调节海马体中的神经元兴奋性,并且还与小胶质细胞激活和神经炎症反应有关。因此,人们对包括癫痫在内的神经系统疾病中的P2X7受体产生了兴趣。研究表明,在长时间癫痫发作(癫痫持续状态)后,大脑受损区域的神经元和胶质细胞中P2X7受体的表达都会升高。在实验性癫痫中,海马体中的P2X7受体表达也会增加。最近的数据表明,缺乏P2X7受体的小鼠对癫痫持续状态的易感性发生改变,并且靶向P2X7受体的药物具有强大的抗惊厥作用。总之,这表明P2X7受体配体可能是难治性癫痫持续状态或药物抵抗性癫痫的有用辅助治疗方法。这篇综述总结了P2X7受体参与癫痫病理生理学的证据以及靶向该受体的药物用于控制癫痫发作的潜力。

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