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.