中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3323-3331.doi: 10.4103/NRR.NRR-D-24-01313

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

RF酰胺神经肽受体家族的生理作用、药物开发和结构特征

  

  • 出版日期:2026-08-18 发布日期:2026-04-23

The arginine–phenylalanine–amide neuropeptide receptor family: Physiological effects, drug development, and structural insight

Yiming Liu1, #, Shirui Jiang2, #, Zhangsong Wu1, 2, Chen Qiu1, Qiaohui Li3, Rui Wang1, Xiaoyi Yan1, Song Wu2, *, Geng Chen1, *, Yang Du1, *   

  1. 1Kobilka Institute of Innovative Drug Discovery, Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong Province, China; 
    2The Huanan Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen, Guangdong Province, China; 
    3Biological Science Research Center, Academy for Advanced Interdisciplinary Studies, Southwest University, Chongqing, China
  • Online:2026-08-18 Published:2026-04-23
  • Contact: Yang Du, PhD, yangdu@cuhk.edu.cn; Geng Chen, PhD, chengeng@cuhk.edu.cn; Song Wu, MD, wusong@szu.edu.cn.
  • Supported by:
    This work was supported by the Shenzhen Science and Technology Innovation Commission, No. JCYJ20220818103009018 (to YD).

摘要:

RF酰胺神经肽(Arginine–Phenylalanine–amide–related peptides, RF-amide peptides)是一类神经肽。其特征是在其C末端具有一个精氨酸-苯丙氨酸酰胺(Arg-Phe-NH₂)基序。RF酰胺肽的受体属于A族G蛋白偶联受体(GPCR),在哺乳动物中,这类受体主要包括焦谷氨酰化RF酰胺肽受体、神经肽FF受体、催乳素释放肽受体和Kisspeptin受体,这个受体家族在疼痛调控,能量稳态,生殖健康等生理和病理过程中发挥着至关重要的作用。RF酰胺神经肽受体靶向药物开发在神经系统中的功能是目前研究的热点之一,特别是在最近有了新的进展。但是,这个主题还有待更新和总结。文章首先总结了RF酰胺神经肽及其受体在神经系统和其他外周器官中的分布,并且还汇总了这些受体通路在多种生理病理功能中的作用。然后,基于结构-活性关系重点讨论了针对RF酰胺神经肽的配体改造情况。最后,通过分析冷冻电镜解析的该蛋白质受体家族高分率结构所提供的信息,进一步讨论了基于结构的靶向药物开发可能性。RF酰胺神经肽受体家族在调节多种生理功能中的积极作用使得其成为有潜力的治疗靶点,然而,由于RF酰胺神经肽与其对应的受体在调节多种信号通路中复杂的关系,蛋白质结构解析方法的介入是十分有必要的,这可以有效阐明配体与受体作用的具体信息,这使得RF酰胺神经肽受体复合物的冷冻电镜结构解析正成为研究者关注的焦点。与此同时,这些工作也将为RF酰胺神经肽受体的配体的优化改造工作提供有力的支持。此外,探索RF酰胺神经肽及其改造物在神经系统中的临床应用也非常重要。


https://orcid.org/0000-0001-5115-0736 (Yang Du); https://orcid.org/0000-0001-6209-301X (Geng Chen); 

https://orcid.org/0000-0003-3504-1630 (Song Wu)

关键词: 食欲调节, RF酰胺神经肽, 药物发现, G 蛋白偶联受体, 神经肽, 疼痛调节, 结构-活性关系

Abstract: The arginine–phenylalanine–amide neuropeptide receptor family comprises a subclass within the G protein-coupled receptor superfamily with crucial roles in physiological regulation. These receptors recognize and bind neuropeptides with an arginine–phenylalanine–amide motif, thereby participating in a variety of biological processes such as energy metabolism, pain perception, and reproductive functions. In this review, we explore the physiological and pathological processes involving these receptors and delve into the structure-activity relationships of their ligand peptides, clarifying the key structural motifs within these neuropeptides that determine their biological activity, pharmacological potency, and receptor selectivity. Particular emphasis is placed on their roles in modulating nociception, regulating appetite, and maintaining reproductive health. Additionally, we discuss the therapeutic potential of structure-based drug design targeting these receptors based on existing cryo-electron microscopy structures. The available structural insights into ligand-binding pockets and G protein–receptor interaction interfaces provide a clear perspective and valuable complement to ligand optimization.

Key words: appetite regulation, arginine–phenylalanine–amide, drug discovery, G protein-coupled receptor,  , neuropeptides, nerve regeneration, pain modulation, structure–activity relationship