Therapeutic Potential of Targeting Prokineticin Receptors in Diseases.

Pharmacol Rev

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.)

Published: November 2023

AI Article Synopsis

  • Prokineticins (PKs) are small peptides discovered two decades ago, now recognized for their various roles as angiogenic, anorectic, proinflammatory agents, and their involvement in different diseases, making them potential biomarkers.
  • PKs interact with two receptors, PKR1 and PKR2, which have unique therapeutic potentials in treating conditions like cardiovascular, metabolic, neural diseases, pain, and cancer.
  • The article reviews the functions of the PK family, highlights knowledge gaps about their receptors and ligands, and suggests that understanding these proteins better could lead to new, safe treatment strategies.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10595023PMC
http://dx.doi.org/10.1124/pharmrev.122.000801DOI Listing

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