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Vincenzi, M.* ; Kremić, A.* ; Jouve, A.* ; Lattanzi, R.* ; Miele, R.* ; Benharouga, M.* ; Alfaidy, N.* ; Migrenne-Li, S.* ; Kanthasamy, A.G.* ; Porcionatto, M.* ; Ferrara, N.* ; Tetko, I.V. ; Desaubry, L.* ; Nebigil, C.G.*

Therapeutic potential of targeting prokineticin receptors in diseases.

Pharmacol. Rev. 75, 1167-1199 (2023)
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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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Publication type Article: Journal article
Document type Review
Keywords Endothelial Growth-factor; Genes-encoding Prokineticin-2; Cell Polyomavirus Infection; Colony-stimulating Factor; Factor Eg-vegf; Kallmann-syndrome; In-vitro; Olfactory-bulb; Mice Lacking; Pharmacological Characterization
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 0031-6997
e-ISSN 1521-0081
Journal Pharmacological reviews
Quellenangaben Volume: 75, Issue: 6, Pages: 1167-1199 Article Number: , Supplement: ,
Publisher American Society for Pharmacology and Experimental Therapeutics (ASPET)
Publishing Place Bethesda, Md.
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503000-001
Grants Sapienza University of Rome
ERA-CVD
National Institute of Environmental Health Sciences
National Institute of Neurological Disorders and Stroke
National Institutes of Health (NIH) National Eye Institute
Fondation de France
DOI 10.1124/pharmrev.122.000801
WOS ID 001098885600004
Scopus ID 85174750998
PubMed ID 37684054
Erfassungsdatum 2023-11-28
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