Melanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding,
inflammation and immune responses,
pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that
melanocortins also have impressive
therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway
hypovolemic, shock;
septic shock; respiratory
arrest; cardiac arrest;
ischemia- and
ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves;
neuropathic pain; toxic neuropathies;
gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of
melanocortins in
neurodegenerative diseases, in particular
Alzheimer's disease. Our aim was (i) to critically reconsider the established extrahormonal effects of
melanocortins (on sexual activity, feeding,
inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of
melanocortins in models of
neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of
melanocortins as life-saving agents in
shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with
melanocortins in different animal models of tissue
ischemia and
ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects.