Scharf Magdalena M, Humphrys Laura J, Berndt Sandra, Di Pizio Antonella, Lehmann Juliane, Liebscher Ines, Nicoli Alessandro, Niv Masha Y, Peri Lior, Schihada Hannes, Schulte Gunnar
Karolinska Institutet, Dept. Physiology & Pharmacology, Sec. Receptor Biology & Signaling, Stockholm, Sweden.
Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
Br J Pharmacol. 2024 Feb 10. doi: 10.1111/bph.16325.
A large portion of the human GPCRome is still in the dark and understudied, consisting even of entire subfamilies of GPCRs such as odorant receptors, class A and C orphans, adhesion GPCRs, Frizzleds and taste receptors. However, it is undeniable that these GPCRs bring an untapped therapeutic potential that should be explored further. Open questions on these GPCRs span diverse topics such as deorphanisation, the development of tool compounds and tools for studying these GPCRs, as well as understanding basic signalling mechanisms. This review gives an overview of the current state of knowledge for each of the diverse subfamilies of understudied receptors regarding their physiological relevance, molecular mechanisms, endogenous ligands and pharmacological tools. Furthermore, it identifies some of the largest knowledge gaps that should be addressed in the foreseeable future and lists some general strategies that might be helpful in this process.
人类GPCR组的很大一部分仍处于未知状态且研究不足，甚至包括GPCR的整个亚家族，如嗅觉受体、A类和C类孤儿受体、粘附GPCR、卷曲蛋白和味觉受体。然而，不可否认的是，这些GPCR具有尚未开发的治疗潜力，值得进一步探索。关于这些GPCR的悬而未决的问题涵盖了多个主题，如去孤儿化、研究这些GPCR的工具化合物和工具的开发，以及对基本信号传导机制的理解。本综述概述了未充分研究的受体的各个不同亚家族在生理相关性、分子机制、内源性配体和药理学工具方面的当前知识状态。此外，它还指出了一些在可预见的未来应解决的最大知识空白，并列出了一些在此过程中可能有用的一般策略。
