Melanocortins, Melanocortin Receptors and Multiple Sclerosis

Abstract

The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cells (lymphocytes and monocytes) and by signaling through CNS cells in regions lacking a mature blood brain barrier are clear. However, additional studies are needed to develop highly effective MCR targeted therapies that directly affect endogenous cells of the CNS, particularly OL, their progenitors and neurons.

Functional Characterization of Melanocortin-3 Receptor In Rainbow Trout (Oncorhynchus Mykiss)

“…The high activation e cacy of ACTH in this study is similar to that of channel cat sh (Yang et al 2019) but is different from that of pigs (Fan et al 2008). As a "primitive" ligand, ACTH (1-24) exhibits a high a nity for MCRs of shes (Klovins et al, 2004b;Li et al, 2016), but a relatively low a nity for MCRs of mammals (Lisak and Benjamins 2017). Our results provide another evidence to support the concept that ACTH may be the "original" ligand for the ancestral melanocortin receptors (Dores and Baron 2011;Dores et al 2014).…”

Functional Characterization of Melanocortin-3 Receptor in a Hibernating Cavefish Onychostoma macrolepis

“…For the cAMP signaling pathway, ACTH (1–24) showed the highest activation efficacy, which is consistent with the results of channel catfish [ 12 ] but different from those of pigs [ 33 ]. ACTH (1–24), as a “primitive” ligand, shows lower and higher affinity to mammals [ 34 ] and fish [ 3 , 35 ], respectively. There is a view that ACTH is the “original” ligand for ancestral MCRs [ 36 , 37 ], and our results supported this hypothesis.…”

Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia–Reperfusion in Rats

“…Earlier it was shown that Semax (1 μM) did not affect cyclic adenosine monophosphate (cAMP) levels in HEK293 cells expressing the human melanocortin 4 receptor (MCR4), but antagonized the cAMP-inducing effect of the melanocortin derivative α-melanocyte-stimulating hormone (α-MSH) in this cells [ 64 ]. Additionally, in models of brain ischaemia and inflammation, α-MSH exhibits strong anti-inflammatory, neurogenic and neuroprotective effects [ 65 , 66 , 67 ]. Therefore, Semax may recapitulate some important neuroprotective actions of the melanocortins.…”