Tomas Lindhal Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University (SYSU), No.628, Zhenyuan Rd., Guangming Dist., Shenzhen 518107, China.
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Cells. 2022 Apr 14;11(8):1334. doi: 10.3390/cells11081334.
G-protein-coupled receptors (GPCRs) remain one of the most successful targets for therapeutic drugs approved by the US Food and Drug Administration (FDA). Many novel orphan GPCRs have been identified by human genome sequencing and considered as putative targets for refractory diseases. Of note, a series of studies have been carried out involving GPCR 158 (or GPR158) since its identification in 2005, predominantly focusing on the characterization of its roles in the progression of cancer and mental illness. However, advances towards an in-depth understanding of the biological mechanism(s) involved for clinical application of GPR158 are lacking. In this paper, we clarify the origin of the GPR158 evolution in different species and summarize the relationship between GPR158 and different diseases towards potential drug target identification, through an analysis of the sequences and substructures of GPR158. Further, we discuss how recent studies set about unraveling the fundamental features and principles, followed by future perspectives and thoughts, which may lead to prospective therapies involving GPR158.
G 蛋白偶联受体（GPCRs）仍然是美国食品和药物管理局（FDA）批准的治疗药物最成功的靶点之一。通过人类基因组测序已经鉴定出许多新型孤儿 GPCRs，并被认为是难治性疾病的潜在靶点。值得注意的是，自 2005 年发现 GPCR158（或 GPR158）以来，已经进行了一系列研究，主要集中在其在癌症和精神疾病进展中的作用的表征上。然而，对于深入了解 GPR158 涉及的生物学机制以实现其临床应用的研究进展有限。在本文中，我们通过分析 GPR158 的序列和亚结构，阐明了不同物种中 GPR158 进化的起源，并总结了 GPR158 与不同疾病之间的关系，以确定潜在的药物靶点。此外，我们还讨论了最近的研究如何着手揭示基本特征和原则，以及未来的展望和思考，这可能会导致涉及 GPR158 的潜在治疗方法。
