Regenerative Nanomedicine (UMR 1260), INSERM, University of Strasbourg, Center of Research in Biomedicine of Strasbourg, Strasbourg, France (M.V., A.K., A.J., L.D., C.G.N.); Department of Physiology and Pharmacology (M.V., R.L.), and Department of Biochemical Sciences "Alessandro Rossi Fanelli" (R.M.), Sapienza University of Rome, Rome, Italy; University Grenoble Alpes, INSERM, CEA, Grenoble, France (M.B., N.A.); Unité de Biologie Fonctionnelle et Adaptative, Université Paris Cité, CNRS, Paris, France (S.M.); Department of Physiology and Pharamacology, Center for Neurologic Disease Research, University of Georgia, Athens, Georgia (A.G.K.); Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil (M.A.P.); Moores Cancer Center, University of California, San Diego, La Jolla, California (N.F.); and Institute of Structural Biology, Helmholtz Munich - German Research Center for Environmental Health (GmbH), Neuherberg, Germany (I.V.T.); and BIGCHEM GmbH, Valerystr. 49, Unterschleissheim, Germany (I.V.T.).
Regenerative Nanomedicine (UMR 1260), INSERM, University of Strasbourg, Center of Research in Biomedicine of Strasbourg, Strasbourg, France (M.V., A.K., A.J., L.D., C.G.N.); Department of Physiology and Pharmacology (M.V., R.L.), and Department of Biochemical Sciences "Alessandro Rossi Fanelli" (R.M.), Sapienza University of Rome, Rome, Italy; University Grenoble Alpes, INSERM, CEA, Grenoble, France (M.B., N.A.); Unité de Biologie Fonctionnelle et Adaptative, Université Paris Cité, CNRS, Paris, France (S.M.); Department of Physiology and Pharamacology, Center for Neurologic Disease Research, University of Georgia, Athens, Georgia (A.G.K.); Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil (M.A.P.); Moores Cancer Center, University of California, San Diego, La Jolla, California (N.F.); and Institute of Structural Biology, Helmholtz Munich - German Research Center for Environmental Health (GmbH), Neuherberg, Germany (I.V.T.); and BIGCHEM GmbH, Valerystr. 49, Unterschleissheim, Germany (I.V.T.)
Pharmacol Rev. 2023 Nov;75(6):1167-1199. doi: 10.1124/pharmrev.122.000801. Epub 2023 Sep 8.
The prokineticins (PKs) were discovered approximately 20 years ago as small peptides inducing gut contractility. Today, they are established as angiogenic, anorectic, and proinflammatory cytokines, chemokines, hormones, and neuropeptides involved in variety of physiologic and pathophysiological pathways. Their altered expression or mutations implicated in several diseases make them a potential biomarker. Their G-protein coupled receptors, PKR1 and PKR2, have divergent roles that can be therapeutic target for treatment of cardiovascular, metabolic, and neural diseases as well as pain and cancer. This article reviews and summarizes our current knowledge of PK family functions from development of heart and brain to regulation of homeostasis in health and diseases. Finally, the review summarizes the established roles of the endogenous peptides, synthetic peptides and the selective ligands of PKR1 and PKR2, and nonpeptide orthostatic and allosteric modulator of the receptors in preclinical disease models. The present review emphasizes the ambiguous aspects and gaps in our knowledge of functions of PKR ligands and elucidates future perspectives for PK research. SIGNIFICANCE STATEMENT: This review provides an in-depth view of the prokineticin family and PK receptors that can be active without their endogenous ligand and exhibits "constitutive" activity in diseases. Their non- peptide ligands display promising effects in several preclinical disease models. PKs can be the diagnostic biomarker of several diseases. A thorough understanding of the role of prokineticin family and their receptor types in health and diseases is critical to develop novel therapeutic strategies with safety concerns.
亲菌素（PKs）大约在 20 年前被发现，是一种能诱导肠道收缩的小肽。如今，它们被确立为参与多种生理和病理生理途径的血管生成、厌食和促炎细胞因子、趋化因子、激素和神经肽。它们的表达改变或突变与多种疾病有关，使它们成为一种潜在的生物标志物。它们的 G 蛋白偶联受体，PKR1 和 PKR2，具有不同的作用，可以作为治疗心血管、代谢和神经疾病以及疼痛和癌症的治疗靶点。本文综述并总结了我们目前对 PK 家族功能的认识，从心脏和大脑的发育到健康和疾病中内稳态的调节。最后，综述总结了内源性肽、合成肽和 PKR1 和 PKR2 的选择性配体以及受体的非肽直立和变构调节剂在临床前疾病模型中的作用。本综述强调了我们对 PKR 配体功能的认识中存在的模糊方面和差距，并阐明了 PK 研究的未来前景。
本综述深入探讨了亲菌素家族及其 PK 受体的作用，这些受体可以在没有内源性配体的情况下发挥作用，并在疾病中表现出“组成型”活性。它们的非肽配体在几种临床前疾病模型中显示出有希望的效果。PKs 可以作为几种疾病的诊断生物标志物。深入了解亲菌素家族及其受体类型在健康和疾病中的作用对于开发具有安全问题的新型治疗策略至关重要。
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