Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives. (January 2017)

• Record Type: Journal Article
• Authors: Giuliani, Daniela; Ottani, Alessandra; Neri, Laura; Zaffe, Davide; Grieco, Paolo; Jochem, Jerzy; Cavallini, Gian Maria; Catania, Anna; Guarini, Salvatore
• Is Part Of: Progress in neurobiology. Volume 148(2017:Jan.)
• Page Start: 40
• Page End: 56
• Publication Date: 2017-01
• Subjects: Aβ β-amyloid -- ACTH adrenocorticotropic hormone -- AD Alzheimer's disease -- BDNF brain-derived neurotrophic factor -- BrdU 5-bromo-2′-deoxyuridine -- CNS central nervous system -- DG dentate gyrus -- ERK extracellular signal-regulated kinases -- HMGB-1 high Mobility Group Box-1 -- JNK c-jun N-terminal kinases -- MSH melanocyte-stimulating hormone -- NDP-α-MSH [Nle4, D-Phe7]α-melanocyte-stimulating hormone -- SAH subarachnoid hemorrhage -- SCI spinal cord injury -- SGZ subgranular zone -- Shh sonic hedgehog -- IL interleukin -- SVZ subventricular zone -- TBI traumatic brain injury -- TNF-α tumor necrosis factor-α; Neurodegenerative diseases -- Pathophysiological mechanisms -- Melanocortin receptor agonists -- Neuroprotection -- Neurogenesis -- Functional recovery; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2016.11.004
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: Melanocortins induce neuroprotection and neurogenesis in neurodegenerative disorders. Melanocortins improve synaptic activity and neurological performance. These effects are mediated by melanocortin MC4 receptors. Abstract: 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.