Catania Anna
Center for Preclinical Investigation, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, 20122 Milano, Italy.
Trends Neurosci. 2008 Jul;31(7):353-60. doi: 10.1016/j.tins.2008.04.002. Epub 2008 Jun 10.
Alpha-melanocyte stimulating hormone (alpha-MSH) and other melanocortins make up a family of endogenous peptides derived from pro-opiomelanocortin. Through binding to five melanocortin receptors (MCR), these peptides exert multiple influences on the host, including anti-inflammatory and immunomodulatory effects. The wide distribution of at least three melanocortin receptor subtypes (MC1R, MC3R and MC4R) in neural, glial and endothelial cells suggests that these receptors could be pharmacological targets for neuroprotective therapies. As a consequence of modulation of NF-kappaB-mediated transcription, melanocortins reduce production of pro-inflammatory agents in brain cells after injury. During brain ischemia, alpha-MSH and other melanocortins exert protective influences with a broad time window. Further, melanocortins rescue neurons subjected to excitotoxic insults, accelerate neurophysiological recovery after spinal cord injury and increase regenerative capacity of peripheral nerves in postlesion repair. Based on their established actions, melanocortins could form a novel class of therapeutic agents for acute and chronic disorders of the nervous system.
α-黑素细胞刺激素（α-MSH）和其他促黑素细胞激素构成了一个源自阿片促黑素皮质素原的内源性肽家族。通过与五种促黑素细胞激素受体（MCR）结合，这些肽对宿主产生多种影响，包括抗炎和免疫调节作用。至少三种促黑素细胞激素受体亚型（MC1R、MC3R和MC4R）在神经、神经胶质和内皮细胞中的广泛分布表明，这些受体可能是神经保护疗法的药理学靶点。作为对NF-κB介导转录调节的结果，促黑素细胞激素可减少损伤后脑细胞中促炎因子的产生。在脑缺血期间，α-MSH和其他促黑素细胞激素在较宽的时间窗内发挥保护作用。此外，促黑素细胞激素可挽救遭受兴奋性毒性损伤的神经元，加速脊髓损伤后的神经生理恢复，并增加损伤后修复过程中外周神经的再生能力。基于其已确定的作用，促黑素细胞激素可形成一类用于治疗急慢性神经系统疾病的新型治疗药物。
