Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives.

Abstract

Melanocortin peptides induce neuroprotection in acute and chronic experimental neurodegenerative conditions. Melanocortins likewise counteract systemic responses to brain injuries. Furthermore, they promote neurogenesis by activating critical signaling pathways. Melanocortin-induced long-lasting improvement in synaptic activity and neurological performance, including learning and memory, sensory-motor orientation and coordinated limb use, has been consistently observed in experimental models of acute and chronic neurodegeneration. Evidence indicates that the neuroprotective and neurogenic effects of melanocortins, as well as the protection against systemic responses to a brain injury, are mediated by brain melanocortin 4 (MC4) receptors, through an involvement of the vagus nerve. Here we discuss the targets and mechanisms underlying the multiple beneficial effects recently observed in animal models of neurodegeneration. We comment on the potential clinical usefulness of melanocortin MC4 receptor agonists as neuroprotective and neuroregenerative agents in ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, and Alzheimer's disease.

• Authors: Daniela Giuliani, Alessandra Ottani, Laura Neri, Davide Zaffe, Paolo Grieco, Jerzy Jochem, Gian Maria Cavallini, Anna Catania, Salvatore Guarini
• Journal: Progress in neurobiology (Prog Neurobiol) Vol. 148 Pg. 40-56 (Jan 2017) ISSN: 1873-5118 [Electronic] England
• PMID: 27916623 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Neuroprotective Agents
• Receptor, Melanocortin, Type 4

Topics

• Animals
• Disease Models, Animal
• Neurodegenerative Diseases (drug therapy, metabolism)
• Neuroprotective Agents (pharmacology)
• Receptor, Melanocortin, Type 4 (agonists, metabolism)