Journal
PROGRESS IN NEUROBIOLOGY
Volume 148, Issue -, Pages 40-56Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pneurobio.2016.11.004
Keywords
Neurodegenerative diseases; Pathophysiological mechanisms; Melanocortin receptor agonists; Neuroprotection; Neurogenesis; Functional recovery
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Funding
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), Roma
- University of Modena and Reggio Emilia, Italy
- Fondazione Cassa di Risparmio di Modena, Italy
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Melanocortin peptides induce neuroprotection in acute and chronic experimental neurodegenerative conditions. Melanocortins likewise counteract systemic responses to brain injuries. Furthermore, they promote neurogenesis by activating critical signaling pathways. Melanocortin-induced long-lasting improvement in synaptic activity and neurological performance, including learning and memory, sensory-motor orientation and coordinated limb use, has been consistently observed in experimental models of acute and chronic neurodegeneration. Evidence indicates that the neuroprotective and neurogenic effects of melanocortins, as well as the protection against systemic responses to a brain injury, are mediated by brain melanocortin 4 (MC4) receptors, through an involvement of the vagus nerve. Here we discuss the targets and mechanisms underlying the multiple beneficial effects recently observed in animal models of neurodegeneration. We comment on the potential clinical usefulness of melanocortin MC4 receptor agonists as neuroprotective and neuroregenerative agents in ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, and Alzheimer's disease. (C) 2016 Elsevier Ltd. All rights reserved.
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