PDF(Pubmed)
Abstract：
Neuropeptides and G protein-coupled receptors (GPCRs) have long been, and continue to be, one of the most popular target classes for drug discovery in CNS disorders, including alcohol use disorder (AUD). Yet, orphaned neuropeptide systems and receptors (oGPCR), which have no known cognate receptor or ligand, remain understudied in drug discovery and development. Orphan neuropeptides and oGPCRs are abundantly expressed within the brain and represent an unprecedented opportunity to address brain function and may hold potential as novel treatments for disease. Here, we describe the current literature regarding orphaned neuropeptides and oGPCRs implicated in AUD. Specifically, in this review, we focus on the orphaned neuropeptide cocaine- and amphetamine-regulated transcript (CART), and several oGPCRs that have been directly implicated in AUD (GPR6, GPR26, GPR88, GPR139, GPR158) and discuss their potential and pitfalls as novel treatments, and progress in identifying their cognate receptors or ligands.
摘要：
神经肽和G蛋白偶联受体(GPCRs)长期以来,并继续，中枢神经系统疾病中最受欢迎的药物发现目标类别之一，包括酒精使用障碍（AUD）。然而，孤儿神经肽系统和受体（OGPCR），没有已知的同源受体或配体，在药物发现和开发方面研究不足。孤儿神经肽和oGPCRs在大脑中大量表达，代表了解决大脑功能的前所未有的机会，并且可能具有作为疾病新疗法的潜力。这里,我们描述了目前有关孤立神经肽和oGPCRs与AUD有关的文献。具体来说,在这次审查中,我们专注于孤儿神经肽可卡因和苯丙胺调节转录本（CART），和几个直接牵涉到AUD的oGPCRs（GPR6，GPR26，GPR88，GPR139，GPR158），并讨论它们作为新疗法的潜力和陷阱，以及识别其同源受体或配体的进展。
