Title:Melanocortins As Innovative Drugs for Ischemic Diseases and Neurodegenerative Disorders: Established Data and Perspectives
Volume: 20
Issue: 6
Author(s): S. Leone, G. Noera and A. Bertolini
Affiliation:
Keywords:
Alzheimer’s disease, amyotrophic lateral sclerosis, heart ischemia/reperfusion, intestinal ischemia/reperfusion, ischemic diseases, melanocortins, miocardial infarction, multiple sclerosis, parkinson’s disease, renal ischemia, respiratory arrest, shock, stroke
Abstract: Ischemic insults and neurodegenerative diseases are by far the leading cause of mortality and disability. Whole-body hypoperfusion,
as it occurs in polytraumatic and hemorrhagic shock, is alike an increasingly frequent condition, especially due to traffic accidents,
wars and acts of terrorism. It is now clearly established that inflammatory processes play a fundamental role in the pathophysiology
of both hypoperfusion/ischemia damage (be it generalized to the whole body, as in the case of shock, or limited to individual organs)
and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis). On the other
hand, concurrent animal and human data show that melanocortin peptides with agonist activity at melanocortin MC3/MC4 receptors are
highly effective in different shock conditions as well as in conditions of ischemia/ischemia-reperfusion of individual organs (heart, brain,
intestine, kidney, etc.), and accumulating evidence indicates that such effects of melanocortins are mostly due to quite peculiar antiinflammatory
mechanisms. Melanocortins have also long been known (i) to exert important neurotrophic effects, not only during fetal
development but also in adulthood, in different animal models of brain lesions; (ii) to reduce the morphological correlates of brain aging;
(iii) to retard the behavioral deficits that develop during the aging process. Moreover, recent data from different laboratories show that after
brain ischemic episodes melanocortins activate the transcription of neurotrophins and their receptors in the cerebral cortex and in the
hippocampus, and increase the proliferation of progenitor neuron cells. The above arguments support the view that pharmacokinetically
suitable agonists at MC3/MC4 melanocortin receptors may represent a completely innovative class of drugs for an effective treatment of
both ischemic and neurodegenerative diseases.
