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: Daniela Giuliani, Letteria Minutoli, Alessandra Ottani, Luca Spaccapelo, Alessandra Bitto, Maria Galantucci, Domenica Altavilla, Francesco Squadrito, Salvatore Guarini
• Journal: Frontiers in neuroendocrinology (Front Neuroendocrinol) Vol. 33 Issue 2 Pg. 179-93 (Apr 2012) ISSN: 1095-6808 [Electronic] United States
• PMID: 22531139 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cardiotonic Agents
• Drugs, Investigational
• Melanocortins
• Neuroprotective Agents
• Receptors, Melanocortin

Topics

• Animals
• Cardiotonic Agents (pharmacology, therapeutic use)
• Drugs, Investigational (pharmacology, therapeutic use)
• Humans
• Hypoxia (drug therapy, pathology)
• Melanocortins (metabolism, pharmacology, therapeutic use)
• Models, Biological
• Neuroprotective Agents (pharmacology, therapeutic use)
• Receptors, Melanocortin (genetics, metabolism, physiology)
• Severity of Illness Index
• Shock (drug therapy, prevention & control)