Clinical Potential of Neuropeptide Y Receptor Ligands in the Treatment of Epilepsy

Meurs, Alfred; Clinckers, Ralph; Ebinger, Guy; Michotte, Yvette; Smolders, Ilse Julia

doi:10.2174/156802607782340975

Cited by 23 publications

(8 citation statements)

References 196 publications

(249 reference statements)

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“…Experiments with Y2 knockout mice and overexpression of the selective Y2 ligand NPY13-36 suggest that Y2 receptor is also involved in the suppression of seizures [74,75]. In line with these studies, Y1 antagonists, and Y2 and Y5 agonists were suggested to have antiepileptic potential [76]. Indeed, a large number of different peptide derivatives of NPY were tested in animal models of epilepsy supporting this suggestion [60].…”

Section: Neuropeptide Ymentioning

confidence: 95%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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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 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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Section: Neuropeptide Ymentioning

confidence: 95%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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“…Development of novel oral and parental drug delivery strategies may allow brain access of NPY receptor ligands in a clinical setting. 30 …”

Section: Npy and Modulation Of Emotion Andmentioning

confidence: 99%

Neuropeptide Y

Benarroch¹

2009

Neurology

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“…Selective NPY receptor antagonists have been developed with the aim of being new treatment for a variety of conditions including anxiety, sleep disorders, eating disorders, in addition to epilepsy (Ortiz et al., 2007; Wiater et al., 2011; Wu et al., 2011; van Raay et al., 2012). However, the barriers to clinical development have been developing compounds that are orally active, have sufficiently long half‐life, and cross the blood–brain barrier (Meurs et al., 2007). One potential approach to overcome these barriers is to use viral‐based gene therapy, focally administered into epileptogenic brain regions that selectively up‐regulate NPY expression.…”

Section: Neuropeptide Modulators Of Synaptic Neurotransmissionmentioning

confidence: 99%

Regulators of synaptic transmission: Roles in the pathogenesis and treatment of epilepsy

2012

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SUMMARYSynaptic transmission is the communication between a presynaptic and a postsynaptic neuron, and the subsequent processing of the signal. These processes are complex and highly regulated, reflecting their importance in normal brain functioning and homeostasis. Sustaining synaptic transmission depends on the continuing cycle of synaptic vesicle formation, release, and endocytosis, which requires proteins such as dynamin, syndapin, synapsin, and synaptic vesicle protein 2A. Synaptic transmission is regulated by diverse mechanisms, including presynaptic modulators of synaptic vesicle formation and release, postsynaptic receptors and signaling, and modulators of neurotransmission.Neurotransmitters released presynaptically can bind to their postsynaptic receptors, the inhibitory c-aminobutyric acid (GABA)ergic receptors or the excitatory glutamate receptors. Once released, glutamate activates a variety of postsynaptic receptors including a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA), kainate, and metabotropic receptors. The activation of the receptors triggers downstream signaling cascades generating a vast array of effects, which can be modulated by a numerous auxiliary regulatory subunits. Moreover, different neuropeptides such as neuropeptide Y, brain-derived neurotrophic factor (BDNF), somatostatin, ghrelin, and galanin, act as regulators of diverse synaptic functions and along with the classic neurotransmitters. Abnormalities in the regulation of synaptic transmission play a critical role in the pathogenesis of numerous brain diseases, including epilepsy. This review focuses on the different mechanisms involved in the regulation of synaptic transmission, which may play a role in the pathogenesis of epilepsy: the presynaptic modulators of synaptic vesicle formation and release, postsynaptic receptors, and modulators of neurotransmission, including the mechanism by which drugs can modulate the frequency and severity of epileptic seizures.

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Clinical Potential of Neuropeptide Y Receptor Ligands in the Treatment of Epilepsy

Cited by 23 publications

References 196 publications

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Neuropeptide Y

Regulators of synaptic transmission: Roles in the pathogenesis and treatment of epilepsy

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