Lisak Robert P, Benjamins Joyce A
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Brain Sci. 2017 Aug 14;7(8):104. doi: 10.3390/brainsci7080104.
The melanocortins and their receptors have been extensively investigated for their roles in the hypothalamo-pituitary-adrenal axis, but to a lesser extent in immune cells and in the nervous system outside the hypothalamic axis. This review discusses corticosteroid dependent and independent effects of melanocortins on the peripheral immune system, central nervous system (CNS) effects mediated through neuronal regulation of immune system function, and direct effects on endogenous cells in the CNS. We have focused on the expression and function of melanocortin receptors in oligodendroglia (OL), the myelin producing cells of the CNS, with the goal of identifying new therapeutic approaches to decrease CNS damage in multiple sclerosis as well as to promote repair. It is clear that melanocortin signaling through their receptors in the CNS has potential for neuroprotection and repair in diseases like MS. Effects of melanocortins on the immune system by direct effects on the circulating cells (lymphocytes and monocytes) and by signaling through CNS cells in regions lacking a mature blood brain barrier are clear. However, additional studies are needed to develop highly effective MCR targeted therapies that directly affect endogenous cells of the CNS, particularly OL, their progenitors and neurons.
黑素皮质素及其受体在丘脑-垂体-肾上腺轴中的作用已得到广泛研究，但在免疫细胞和下丘脑轴以外的神经系统中的研究较少。本综述讨论了黑素皮质素对外周免疫系统的皮质类固醇依赖性和非依赖性作用、通过免疫系统功能的神经元调节介导的中枢神经系统（CNS）效应以及对CNS内源性细胞的直接作用。我们重点关注了少突胶质细胞（OL）中黑素皮质素受体的表达和功能，OL是CNS中产生髓磷脂的细胞，目的是确定减少多发性硬化症中CNS损伤以及促进修复的新治疗方法。很明显，黑素皮质素通过其在CNS中的受体发出信号，在MS等疾病中具有神经保护和修复的潜力。黑素皮质素对循环细胞（淋巴细胞和单核细胞）的直接作用以及通过缺乏成熟血脑屏障区域的CNS细胞发出信号对免疫系统的影响是明确的。然而，需要进一步研究以开发直接影响CNS内源性细胞，特别是OL、其祖细胞和神经元的高效MCR靶向疗法。
