Abstract
Epilepsy is a neurological disease affecting more than 50 million individuals worldwide. Notwithstanding the availability of a broad array of antiseizure drugs (ASDs), 30% of patients suffer from pharmacoresistant epilepsy. This highlights the urgent need for novel therapeutic options, preferably with an emphasis on new targets, since “me too” drugs have been shown to be of no avail. One of the appealing novel targets for ASDs is the ghrelin receptor (ghrelin-R). In epilepsy patients, alterations in the plasma levels of its endogenous ligand, ghrelin, have been described, and various ghrelin-R ligands are anticonvulsant in preclinical seizure and epilepsy models. Up until now, the exact mechanism-of-action of ghrelin-R-mediated anticonvulsant effects has remained poorly understood and is further complicated by multiple downstream signaling pathways and the heteromerization properties of the receptor. This review compiles current knowledge, and discusses the potential mechanisms-of-action of the anticonvulsant effects mediated by the ghrelin-R.
Highlights
Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures [1].With approximately 50 million patients, it is one of the most common neurological diseases worldwide [2]
The acylation is either an octanoylation or decanoylation [33,34]. This action is followed by further processing of the 94-amino acid (AA)-long acylated pro-ghrelin by prohormone convertases 1/3 (PC1/3), which results in acylated ghrelin (AG), and yields the mature peptide, obestatin [35]
Most studies show lower ghrelin levels in patients suffering from epilepsy, or lower ghrelin levels after a seizure
Summary
Epilepsy is a neurological disease characterized by spontaneous and recurrent seizures [1]. 30% of patients suffer from pharmacoresistant epilepsy [2], of which a large proportion has temporal lobe epilepsy (TLE) [3,4]. This highlights the urgent need for the development of novel pharmacological treatment options. One of these potential options is the orexigenic peptide, ghrelin. Ghrelin confers a regulatory role on growth hormone (GH) release [19], is implicated in learning and memory [21,22,23], modulates motivation and reward [24,25], and regulates the stress response (reviewed in [26]). Up until now, the exact mechanism-of-action remains to be understood
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