Therapeutic Potential of Targeting Prokineticin Receptors in Diseases,Pharmacological Reviews

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Therapeutic Potential of Targeting Prokineticin Receptors in Diseases
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2023-11-01 , DOI: 10.1124/pharmrev.122.000801
Martina Vincenzi ₁ , Amin Kremić ₁ , Appoline Jouve ₁ , Roberta Lattanzi ₁ , Rossella Miele ₁ , Mohamed Benharouga ₁ , Nadia Alfaidy ₁ , Stephanie Migrenne-Li ₁ , Anumantha G Kanthasamy ₁ , Marimelia Porcionatto ₁ , Napoleone Ferrara ₁ , Igor V Tetko ₁ , Laurent Désaubry ₁ , Canan G Nebigil ₂

Affiliation

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.)

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.

中文翻译：

靶向前动力蛋白受体在疾病中的治疗潜力

大约 20 年前，人们发现了前动力素 (PK)，它是诱导肠道收缩的小肽。如今，它们被确定为参与多种生理和病理生理途径的血管生成、食欲和促炎细胞因子、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。本文回顾并总结了我们目前对 PK 家族功能的了解，从心脏和大脑的发育到健康和疾病稳态的调节。最后，该综述总结了内源性肽、合成肽以及 PKR1 和 PKR2 的选择性配体以及受体的非肽直立性和变构调节剂在临床前疾病模型中的既定作用。本综述强调了我们对 PKR 配体功能知识中的模糊性和差距，并阐明了 PK 研究的未来前景。

更新日期：2023-10-18

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