Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; University of Vienna, Faculty of Chemistry, Institute of Biological Chemistry, Vienna, Austria.
Biochem Pharmacol. 2020 Nov;181:114129. doi: 10.1016/j.bcp.2020.114129. Epub 2020 Jun 30.
Neuropeptides are signalling molecules mainly secreted from neurons that act as neurotransmitters or peptide hormones to affect physiological processes and modulate behaviours. In humans, neuropeptides are implicated in numerous diseases and understanding their role in physiological processes and pathologies is important for therapeutic development. Teasing apart the (patho)physiology of neuropeptides remains difficult due to ligand and receptor promiscuity and the complexity of the signalling pathways. The current approach relies on a pharmacological toolbox of agonists and antagonists displaying high selectivity for independent receptor subtypes, with the caveat that only few selective ligands have been discovered or developed. Animal venoms represent an underexplored source for novel receptor subtype-selective ligands that could aid in dissecting human neuropeptide signalling systems. Multiple endogenous-like neuropeptides as well as peptides acting on neuropeptide receptors are present in venoms. In this review, we summarise current knowledge on neuropeptides and discuss venoms as a source for ligands targeting neuropeptide signalling systems.
神经肽是主要由神经元分泌的信号分子，作为神经递质或肽类激素发挥作用，影响生理过程并调节行为。在人类中，神经肽与许多疾病有关，了解它们在生理过程和病理中的作用对于治疗药物的开发很重要。由于配体和受体的混杂性以及信号通路的复杂性，神经肽的（病理）生理学仍然难以解析。目前的方法依赖于具有高选择性的激动剂和拮抗剂的药理学工具包，用于独立的受体亚型，但其缺点是仅发现或开发了少数选择性配体。动物毒液是一种尚未充分开发的新型受体亚型选择性配体来源，可以帮助解析人类神经肽信号系统。毒液中存在多种内源性类似神经肽以及作用于神经肽受体的肽。在这篇综述中，我们总结了目前关于神经肽的知识，并讨论了毒液作为靶向神经肽信号系统的配体的来源。
