In:
Current Neuropharmacology, Bentham Science Publishers Ltd., Vol. 21, No. 12 ( 2023-12), p. 2376-2394
Abstract:
Amyotrophic lateral sclerosis (ALS) arises from neuronal death due to complex interactions
of genetic, molecular, and environmental factors. Currently, only two drugs, riluzole and edaravone, have been approved to slow the progression of this disease. However, ghrelin and other ligands of the
GHS-R1a receptor have demonstrated interesting neuroprotective activities that could be exploited in this pathology. Ghrelin, a 28-amino acid hormone, primarily synthesized and secreted by oxyntic cells
in the stomach wall, binds to the pituitary GHS-R1a and stimulates GH secretion; in addition, ghrelin is endowed with multiple extra endocrine bioactivities. Native ghrelin requires esterification with octanoic
acid for binding to the GHS-R1a receptor; however, this esterified form is very labile and represents less than 10% of circulating ghrelin. A large number of synthetic compounds, the growth hormone
secretagogues (GHS) encompassing short peptides, peptoids, and non-peptidic moieties, are capable of mimicking several biological activities of ghrelin, including stimulation of GH release, appetite,
and elevation of blood IGF-I levels. GHS have demonstrated neuroprotective and anticonvulsant effects in experimental models of pathologies both in vitro and in vivo. To illustrate, some GHS, currently
under evaluation by regulatory agencies for the treatment of human cachexia, have a good safety profile and are safe for human use. Collectively, evidence suggests that ghrelin and cognate GHS
may constitute potential therapies for ALS.
Type of Medium:
Online Resource
ISSN:
1570-159X
DOI:
10.2174/1570159X20666220915103613
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2023
detail.hit.zdb_id:
2119376-9
