title: Multiple beneficial effects of melanocortin MC4receptor 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 MC4receptor agonists as neuroprotective and neuroregenerative agents in ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, and Alzheimer's disease.
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giuliani
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ottani
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Neri
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Zaffe
authors.affiliation: Department of Pharmacy, University of Napoli "Federico II", Napoli, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.affiliation: Department of Basic Medical Sciences, School of Public Health in Bytom, Medical University of Silesia, Katowice, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jochem
authors.affiliation: Department of Ophthalmology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Cavallini
authors.affiliation: Center for Preclinical Surgical Research, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Catania
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: salvatore.guarini@unimore.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guarini
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D044105:Receptor, Melanocortin, Type 4
keywords: Functional recovery; Melanocortin receptor agonists; Neurodegenerative diseases; Neurogenesis; Neuroprotection; Pathophysiological mechanisms