title: Melanocortins as potential therapeutic agents in severe hypoxic conditions.
abstract: Melanocortin peptides with the adrenocorticotropin/melanocyte-stimulating hormone (ACTH/MSH) sequences and synthetic analogs have protective and life-saving effects in experimental conditions of circulatory shock, myocardial ischemia, ischemic stroke, traumatic brain injury, respiratory arrest, renal ischemia, intestinal ischemia and testicular ischemia, as well as in experimental heart transplantation. Moreover, melanocortins improve functional recovery and stimulate neurogenesis in experimental models of cerebral ischemia. These beneficial effects of ACTH/MSH-like peptides are mostly mediated by brain melanocortin MC(3)/MC(4) receptors, whose activation triggers protective pathways that counteract the main ischemia/reperfusion-related mechanisms of damage. Induction of signaling pathways and other molecular regulators of neural stem/progenitor cell proliferation, differentiation and integration seems to be the key mechanism of neurogenesis stimulation. Synthesis of stable and highly selective agonists at MC(3) and MC(4) receptors could provide the potential for development of a new class of drugs for a novel approach to management of severe ischemic diseases.
authors.affiliation: Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giuliani
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ottani
authors.forename: Luca
authors.initials: L
authors.lastname: Spaccapelo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Maria
authors.initials: M
authors.lastname: Galantucci
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guarini
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology; D053486:Melanocortins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D044101:Receptors, Melanocortin / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012720:Severity of Illness Index; D012769:Shock / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D002316:Cardiotonic Agents; D015507:Drugs, Investigational; D053486:Melanocortins; D018696:Neuroprotective Agents; D044101:Receptors, Melanocortin