What is it about?

A number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and 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. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration 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 neuropeptides within the central nervous system will also be discussed.

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Why is it important?

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.

Perspectives

Neuropeptide receptors represent very promising novel targets for drug development in general because of the potentially low side-effects and because they possess the pharmacologically least exploited G-protein receptors. In particular, the endogenous functions of neuropeptides, their sustained and specific influence on neuronal excitation and gene transcription make them appealing for the development of anti-epileptic drugs.

Dr Zsolt Kovacs
Eötvös Loránd University

Read the Original

This page is a summary of: Receptors of Peptides as Therapeutic Targets in Epilepsy Research, Current Medicinal Chemistry, January 2014, Bentham Science Publishers,
DOI: 10.2174/0929867320666131119154018.
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