Giuliani Daniela, Ottani Alessandra, Neri Laura, Zaffe Davide, Grieco Paolo, Jochem Jerzy, Cavallini Gian Maria, Catania Anna, Guarini Salvatore
Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
Prog Neurobiol. 2017 Jan;148:40-56. doi: 10.1016/j.pneurobio.2016.11.004. Epub 2016 Dec 1.
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 (MC) 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 MC receptor agonists as neuroprotective and neuroregenerative agents in ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, spinal cord injury, and Alzheimer's disease.
促黑素肽在急性和慢性实验性神经退行性疾病中可诱导神经保护作用。促黑素同样可对抗对脑损伤的全身反应。此外，它们通过激活关键信号通路促进神经发生。在急性和慢性神经退行性疾病的实验模型中，一直观察到促黑素诱导的突触活动和神经功能的持久改善，包括学习和记忆、感觉运动定向以及肢体协调使用。有证据表明，促黑素的神经保护和神经发生作用，以及对脑损伤全身反应的保护作用，是通过迷走神经介导的脑促黑素4（MC）受体实现的。在此，我们讨论了最近在神经退行性疾病动物模型中观察到的多种有益作用的靶点和机制。我们评论了促黑素MC受体激动剂作为神经保护和神经再生剂在缺血性中风、蛛网膜下腔出血、创伤性脑损伤、脊髓损伤和阿尔茨海默病中的潜在临床应用价值。
