Melanocortins and the Treatment of Nervous System Disease: Potential Relevance to the Skin?

For several decades melanocortins have been implicated in the modulation of brain function. More recently, this idea has been supported by the identification and cloning of melanocortin (MC) receptors in the nervous system. MCs stimulate axonal growth in fetal neural tissue or in neural cell lines in culture. This feature was utilized in screening their neurotrophic or neuroprotection potential in animal studies of nervous system disease (peripheral nerve and spinal cord trauma, toxic and metabolic neuropathies, EAN, EAE, etc.). Some of these effects may be mediated by MC4 receptor activation, although as yet unknown receptors may also be involved (for instance, protection by Org 2766). To what extent MC-nervous system effects are related to known effects of MCs in skin- and neuro-immune systems, remains to be discovered. Nevertheless, it is of interest to note that activation of brain MC4 receptors profoundly affects care behavior for the body surface (skin and fur). The excessive grooming response in rodents exhibits a remarkable functional correlation with MSH activity in a brain-skin axis.