Receptors of Peptides as Therapeutic Targets in Epilepsy Research
Receptors of Peptides as Therapeutic Targets in Epilepsy Research
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DOI：
10.2174/0929867320666131119154018
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发表时间：
2014-02-01
影响因子：
4.1
通讯作者：
Kovacs, Z.
中科院分区：
文献类型：
--
作者：
Dobolyi, A.;Kekesi, K. A.;Kovacs, Z.
神经肽是参与突触传递调节的信号分子。神经肽储存在致密的核心突触囊泡中，其释放需要深刻的兴奋。仅在细胞外空间，神经肽作用于G蛋白偶联受体，以在突触前和突触后发挥相对缓慢的作用。因此，神经肽调节剂是影响癫痫发作期间过度兴奋的癫痫组织的理想候选者。事实上，许多神经肽具有与癫痫有关的受体，其中许多被认为参与内源性神经保护作用。海马是颞叶癫痫最常见的发作部位，其神经肽受体作为潜在的抗癫痫靶点受到了最大的关注。本文就海马神经肽受体、生长抑素、神经肽Y、甘丙肽、强啡肽、脑啡肽、P物质、胆囊收缩素、血管活性肠肽以及生长激素释放肽、血管紧张素、促肾上腺皮质激素、促甲状腺激素释放激素、催产素、血管加压素等神经肽受体与癫痫的关系作一综述。通过口服施用肽作为药物来激活和抑制受体通常是无效的，因为生物利用度低：肽快速降解和不充分穿透血脑屏障。神经肽受体的非肽激动剂和拮抗剂的开发以及基因治疗方法导致中枢神经系统内的激动剂和拮抗剂的局部生产的最新进展也将进行讨论。
Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre- and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have receptors implicated in epilepsy and many of them are considered to participate in endogenous neuroprotective actions. Neuropeptide receptors, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic targets. Receptors of hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and receptors of some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Activation and inhibition of receptors by oral application of peptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration of peptides through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of agonists and antagonists within the central nervous system will also be discussed.