Department of Biomedical Sciences, School of Medicine, Debre Markos University, Debre Markos, Ethiopia.
Ann N Y Acad Sci. 2023 Sep;1527(1):30-41. doi: 10.1111/nyas.15048. Epub 2023 Aug 1.
The melanocortin signaling system consists of the melanocortin peptides, their distinctive receptors, accessory proteins, and endogenous antagonists. Melanocortin peptides are small peptide hormones that have been studied in a variety of physiological and pathological conditions. There are five types of melanocortin receptors, and they are distributed within the central nervous system and in several tissues of the periphery. The G protein-coupled melanocortin receptors typically signal through adenylyl cyclase and other downstream signaling pathways. Depending on the ligand, surface expression of melanocortin receptor, receptor occupancy period, related proteins, the type of cell, and other parameters, the signaling pathways are complicated and pleiotropic. While it is known that all five melanocortin receptors are coupled to Gs, they can also occasionally couple to Gq or Gi. Both direct and indirect neuroprotection are induced by the melanocortin signaling system. Targeting several of the components of the melanocortin signaling system (ligands, receptors, accessory proteins, signaling effectors, and regulators) may provide therapeutic opportunities. Activation of the melanocortin system improves different functional traits in neurodegenerative diseases. There is a potential for additional melanocortin system interventions by interfering with dimerization or dissociation. This review aims to discuss the melanocortin receptor signaling system and its role in neuroprotection, as well as its therapeutic potential.
黑素皮质素信号系统由黑素皮质素肽、其独特的受体、辅助蛋白和内源性拮抗剂组成。黑素皮质素肽是已在多种生理和病理条件下进行研究的小肽类激素。有五种类型的黑素皮质素受体，它们分布在中枢神经系统和外周的几种组织中。G 蛋白偶联的黑素皮质素受体通常通过腺苷酸环化酶和其他下游信号通路进行信号转导。根据配体、黑素皮质素受体的表面表达、受体占据期、相关蛋白、细胞类型和其他参数的不同，信号通路是复杂和多效的。虽然已知所有五种黑素皮质素受体都与 Gs 偶联，但它们偶尔也与 Gq 或 Gi 偶联。黑素皮质素信号系统诱导直接和间接的神经保护。针对黑素皮质素信号系统的几个组成部分（配体、受体、辅助蛋白、信号效应器和调节剂）可能提供治疗机会。激活黑素皮质素系统可改善神经退行性疾病中的不同功能特征。通过干扰二聚体或解离，可能会有额外的黑素皮质素系统干预。本综述旨在讨论黑素皮质素受体信号系统及其在神经保护中的作用及其治疗潜力。
