Article
Chemistry, Medicinal
Stefan Wagner, Fernando de Moura Gatti, Daniel G. Silva, Natalia V. Ortiz Zacarias, Annelien J. M. Zweemer, Sven Hermann, Monica De Maria, Michael Koch, Christina Weiss, Dirk Schepmann, Laura H. Heitman, Nuska Tschammer, Klaus Kopka, Anna Junker
Summary: In this study, a series of highly selective CCR2 antagonists were designed and synthesized as F-18-labeled PET tracers. The most potent and selective candidate was applied in vivo in a biodistribution study, showing promising potential for further preclinical development. This compound represents the first potential nonpeptidic PET tracer for imaging of CCR2 receptors.
Review
Pharmacology & Pharmacy
Hossein Hemmatazad, Martin D. Berger
Summary: CCR5 plays a crucial role in cancer progression by modulating immune response and promoting tumor cell proliferation and invasion. CCR5 antagonists show promising efficacy in preclinical tumor models, indicating the potential of CCR5 as a therapeutic target for cancer beyond immune-checkpoint inhibitors.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Cell Biology
Dylan Scott Eiger, Noelia Boldizsar, Christopher Cole Honeycutt, Julia Gardner, Sudarshan Rajagopal
Summary: The human chemokine system consists of numerous chemokine ligands and receptors that regulate a wide range of cellular functions and biological processes. These interactions display biased agonism, where different ligands binding to the same receptor can lead to distinct biological effects through different pathways, modulated by changes in ligand, receptor, or specific cellular context. Enhanced understanding of biased agonism in the chemokine system may transform understanding of biased signaling across all GPCR subtypes and lead to development of pharmaceuticals with increased therapeutic efficacy and safer side effect profiles.
CELLULAR SIGNALLING
(2021)
Article
Chemistry, Medicinal
Robert J. Cherney, Prakash Anjanappa, Kumaravel Selvakumar, Douglas G. Batt, Gregory D. Brown, Anne Rose, Ragini Vuppugalla, Jing Chen, Jian Pang, Songmei Xu, Melissa Yarde, Andrew J. Tebben, Venkatram Reddy Paidi, Mary Ellen Cvijic, Arvind Mathur, Joel C. Barrish, Sandhya Mandlekar, Qihong Zhao, Percy H. Carter
Summary: Compound 3, identified as a potent and selective CCR2/5 dual antagonist, demonstrated excellent permeability and stability in vitro, as well as promising pharmacokinetic properties in animal studies, ultimately leading to its selection as a clinical candidate.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Virology
Alexandre P. Fernandes, Ana Agueda-Pinto, Ana Pinheiro, Hugo Rebelo, Pedro J. Esteves
Summary: The chemokine receptors CCR2 and CCR5 have undergone extensive gene conversion in multiple bat species. Bats are known to be reservoirs for viruses, and these results suggest that chimeric CCR2-CCR5 genes may provide a selective advantage against viruses that rely on these receptors.
Article
Pharmacology & Pharmacy
Natalie E. Jasiewicz, Adam D. Brown, Michael Deci, Silvina Matysiak, H. Shelton Earp, Juliane Nguyen
Summary: In this study, an antibody-derived scFv that targets the second extracellular loop (ECL2) of CCR2 was identified using phage display. The blocking of ECL2 was found to inhibit macrophage migration and promote M1 inflammatory cytokine production as effectively as lipopolysaccharide (LPS).
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Critical Care Medicine
Sigal Liraz-Zaltsman, Yael Friedman-Levi, Dalia Shabashov-Stone, Galit Gincberg, Dana Atrakcy-Baranes, Mary Teena Joy, S. Thomas Carmichael, Alcino J. Silva, Esther Shohami
Summary: Inhibition of CCR5 signaling has been shown to have neuroprotective effects after traumatic brain injury, reducing lesion size, inflammation, and increasing ERK phosphorylation. Increased expression of both CCR5 and CXCR4 was observed in cortical cells 3 to 11 days post-injury, suggesting a potential therapeutic window for intervention.
JOURNAL OF NEUROTRAUMA
(2021)
Article
Biology
Nana Zhang, Haibo Zhu, Zijian Li, Erdan Dong
Summary: The biased ligand Higenamine acts as a novel beta-arrestin-biased ligand by inducing ERK1/2 phosphorylation via EGFR transactivation. Its action is dependent on beta-arrestin1/2 and inhibits Doxorubicin-induced cardiomyocyte apoptosis. These findings provide insight into Higenamine's potential diagnostic and therapeutic applications.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Materials Science, Biomaterials
Xin Zhao, Fang Yin, Luoqin Fu, Yingyu Ma, Luyi Ye, Yilin Huang, Weijiao Fan, Wenxue Gao, Yu Cai, Xiaozhou Mou
Summary: The study shows that garlic-derived exosome-like nanovesicles (GaELNVs) can improve liver injury, inhibit inflammatory eruption, reduce inflammatory cells infiltration, and affect proteins related to energy metabolism and autophagy occurrence. GaELNVs also have the ability to decrease the recruitment of circulating monocytes to the liver and inhibit macrophage infiltration.
BIOMATERIALS ADVANCES
(2023)
Article
Neurosciences
Yael Friedman-Levi, Sigal Liraz-Zaltsman, Chen Shemesh, Kinneret Rosenblatt, Efrat L. Kesner, Galit Gincberg, S. Thomas Carmichael, Alcino J. Silva, Esther Shohami
Summary: Blocking CCR5 and CXCR4 after closed head injury (CHI) enhances tissue preservation, increases levels of synaptic cognition-related signaling molecules, and promotes neurobehavioral recovery. These findings suggest that the drugs used in this study, which are FDA approved and in clinical use, should be considered for translational research in TBI patients.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Wei Bin Fang, Diana Sofia Acevedo, Curtis Smart, Brandon Zinda, Nadia Alissa, Kyle Warren, Garth Fraga, Li-Ching Huang, Yu Shyr, Wei Li, Lu Xie, Vincent Staggs, Yan Hong, Fariba Behbod, Nikki Cheng
Summary: DCIS is the most common type of pre-invasive breast cancer in women, with most cases unlikely to progress to invasive breast cancer. Increased CCL2/CCR2 signaling in breast tissue is associated with DCIS progression, potentially serving as a signature to predict the likelihood of DCIS progressing to IDC.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Punit Upadhyaya, Johanna Lahdenranta, Kristen Hurov, Sailaja Battula, Rachel Dods, Eric Haines, Marianna Kleyman, Julia Kristensson, Jessica Kublin, Rachid Lani, Jun Ma, Gemma Mudd, Elizabeth Repash, Katerine Van Rietschoten, Tom Stephen, Fanglei You, Helen Harrison, Liuhong Chen, Kevin McDonnell, Philip Brandish, Nicholas Keen
Summary: Linking Bicycles against costimulatory receptors (e.g., CD137) to Bicycles against tumor antigens (e.g., EphA2) created potent agonists that selectively activated the receptors in the presence of tumor cells expressing these antigens.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
M. Darsaraee, S. Kaveh, A. Mani-Varnosfaderani, M. S. Neiband
Summary: CC chemokine receptors (CCRs) are crucial in the onset and progression of life-threatening diseases. This study aimed to establish structure-activity relationship models for CCR inhibitors using machine learning techniques. By analyzing a large dataset and calculating molecular descriptors, discriminatory features were identified for differentiating active and inactive molecules and modeling inhibitor selectivity towards different CCRs. The developed models showed good reliability and predictability, and achieved high performance in large-scale screening.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Fisheries
Liping Zhou, Zhouyan Liu, Zhihong Zheng, Defu Yao, Yongzhen Zhao, Xiuli Chen, Yueling Zhang, Jude Juventus Aweya
Summary: It has been found that PvCCR1 and PvCCR5 play key roles in the immune response of shrimp and are essential for shrimp survival.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2023)
Article
Neurosciences
Beatrice Paola Festa, Farah H. Siddiqi, Maria Jimenez-Sanchez, Hyeran Won, Matea Rob, Alvin Djajadikerta, Eleanna Stamatakou, David C. Rubinsztein
Summary: In neurodegenerative diseases, activated microglia secrete pro-inflammatory factors, disrupting neuronal autophagy and protein clearance. The microglia-derived CCL-3/-4/-5 activate neuronal CCR5, leading to mTORC1 activation and autophagy dysfunction. Upregulation of CCR5 and its chemokines in mouse models suggests their role in the early phases of Huntington's disease (HD) and tauopathy. Inhibiting CCR5 can rescue autophagy dysfunction and improve HD and tau pathologies in mouse models.
Article
Multidisciplinary Sciences
Marjorie Damian, Veronique Pons, Pedro Renault, Celine M'Kadmi, Bartholome Delort, Lucie Hartmann, Ali I. Kaya, Maxime Louet, Didier Gagne, Khoubaib Ben Haj Salah, Severine Denoyelle, Gilles Ferry, Jean A. Boutin, Renaud Wagner, Jean-Alain Fehrentz, Jean Martinez, Jacky Marie, Nicolas Floquet, Celine Gales, Sophie Mary, Heidi E. Hamm, Jean-Louis Baneres
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Cardiac & Cardiovascular Systems
Celine Guilbeau-Frugier, Marie Cauquil, Clement Karsenty, Olivier Lairez, Camille Dambrin, Bruno Payre, Herve Cassard, Claudie Josse, Marie-Helene Seguelas, Sophie Allart, Maxime Branchereau, Christophe Heymes, Franck Mandel, Marie-Bernadette Delisle, Atul Pathak, Etienne Dague, Jean-Michel Senard, Celine Gales
CARDIOVASCULAR RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Cedric Garcia, Agnes Maurel-Ribes, Michel Nauze, Du N'Guyen, Laurent O. Martinez, Bernard Payrastre, Jean-Michel Senard, Celine Gales, Veronique Pons
CELLULAR AND MOLECULAR LIFE SCIENCES
(2019)
Article
Rehabilitation
Florent Besnier, Marc Labrunee, Lisa Richard, Florence Faggianelli, Helene Kerros, Laurent Soukarie, Marc Bousquet, Jean-Louis Garcia, Atul Pathak, Celine Gales, Thibaut Guiraud, Jean Michel Senard
ANNALS OF PHYSICAL AND REHABILITATION MEDICINE
(2019)
Article
Multidisciplinary Sciences
Marc Kermorgant, Jennifer Ben Salem, Julien Santelli, Denis Calise, Anne-Cecile Oster, Olivier Lairez, Christophe Coudret, Marc Verelst, Celine Gales, Jean-Michel Senard, Francis Beaudry, Anne Pavy-Le Traon, Clement Roux, Robert Mauricot, Dina N. Arvanitis
Article
Immunology
Saria Mcheik, Nils Van Eeckhout, Cedric De Poorter, Celine Gales, Marc Parmentier, Jean-Yves Springael
FRONTIERS IN IMMUNOLOGY
(2019)
Review
Endocrinology & Metabolism
Digne Tembely, Auberi Henry, Laetitia Vanalderwiert, Kevin Toussaint, Amar Bennasroune, Sebastien Blaise, Herve Sartelet, Stephane Jaisson, Celine Gales, Laurent Martiny, Laurent Duca, Beatrice Romier-Crouzet, Pascal Maurice
Summary: The incidence of cardiovascular diseases is increasing due to the aging population, which has a major influence on the vascular tree. Aging leads to changes in the morphology and function of the arterial wall, as well as remodeling of the vascular extracellular matrix. The release of elastin-derived peptides (EDPs) from elastin degradation products is a characteristic feature of aged conduit arteries. These EDPs not only affect the mechanical properties of arteries but also modulate the development and progression of various vascular and metabolic diseases. The elastin receptor complex (ERC), which contains elastin-binding protein, protective protein/cathepsin A, and neuraminidase-1 (NEU1), plays a crucial role in mediating the biological effects of these peptides. This review provides an overview of the consequences of aging on the vasculature and the release of EDPs, discusses the composition and signaling pathways of the ERC, and explores the pharmacological strategies targeting ERC activation. Additionally, it highlights the emerging regulatory functions of the ERC through desialylation of membrane glycoproteins by NEU1 and its potential implication in receptor transactivation.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Hematology
Alice Abelanet, Marion Camoin, Sebastien Rubin, Pauline Bougaran, Valentin Delobel, Mathieu Pernot, Isabelle Forfar, Celine Guilbeau-Frugier, Celine Gales, Marie Lise Bats, Marie-Ange Renault, Pascale Dufourcq, Thierry Couffinhal, Cecile Duplaa
Summary: By studying the specific endothelial dysfunction, we found that an increase of endothelial permeability is responsible for mediating diastolic dysfunction pathophysiology and for aggravating detrimental effects of a high-fat diet on cardiac inflammation and metabolism.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Biology
Etienne Dague, Veronique Pons, Alexandre Roland, Jean-Marc Azais, Silvia Arcucci, Veronique Lachaize, Samuel Velmont, Emmanuelle Trevisiol, Du N'Guyen, Jean-Michel Senard, Celine Gales
Summary: This article reveals the unfolding process of G-protein coupled receptors on the surface of living mammalian cells using atomic force microscopy-based single molecule force spectroscopy. The results show the existence of different receptor populations depending on specificity and expression levels, and the spatial organization of the receptors is determined by the size of the oligomers, which can be reshaped by receptor activity.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Veronique Pons, Cedric Garcia, Naomi Tidten-Luksch, Aengus Mac Sweeney, Eva Caroff, Celine Gales, Markus A. Riederer
Summary: This study demonstrates the inverse agonistic effect of Selatogrel on the P2Y12 receptor, which is more potent than Ticagrelor. Selatogrel stabilizes the inactive state of the receptor and prevents ADP binding, thereby inhibiting platelet activation.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biology
Agnes Ribes, Cedric Garcia, Marie-Pierre Gratacap, Evi Kostenis, Laurent O. Martinez, Bernard Payrastre, Jean-Michel Senard, Celine Gales, Veronique Pons
Summary: This study investigated the pharmacology of P2Y(1)-R signaling in various cells and platelets and found that P2Y(1)-R is constitutively active in physiological conditions. The study also identified P2Y(1)-R antagonists that can inhibit this constitutive activation. These findings suggest that targeting P2Y(1)-R constitutive activation could be a promising strategy for antiplatelet therapy.
Expression of Concern
Cell Biology
Erika Peverelli, Marta Busnelli, Eleonora Vitali, Elena Giardino, Celine Gales, Andrea G. Lania, Paolo Beck-Peccoz, Bice Chini, Giovanna Mantovani, Anna Spada
JOURNAL OF CELL SCIENCE
(2022)
Article
Biology
Clement Karsenty, Celine Guilbeau-Frugier, Gael Genet, Marie-Helene Seguelas, Philippe Alzieu, Olivier Cazorla, Alexandra Montagner, Yuna Blum, Caroline Dubroca, Julile Maupoint, Blandine Tramunt, Marie Cauquil, Thierry Sulpice, Sylvain Richard, Silvia Arcucci, Remy Flores-Flores, Nicolas Pataluch, Romain Montoriol, Pierre Sicard, Antoine Deney, Thierry Couffinhal, Jean-Michel Senard, Celine Gales
Summary: The study found that the development of cardiac crests in cardiomyocytes occurs between postnatal day 20 and day 60, and plays a role in relaxation function of the heart. They identified ephrin-B1 as a molecular determinant of crest maturation and diastolic function. This research highlights the importance of crest maturity in the heart and its implications for cardiac function.
Article
Biology
Ophelie Helissen, Marc Kermorgant, Sebastien Dejean, Aurelie Mercadie, Sophie Le Gonidec, Rana Zahreddine, Denis Calise, Nathalie Nasr, Celine Gales, Dina N. Arvanitis, Anne Pavy-Le Traon
Summary: The kinetics of cardiovascular adaptation and its regulation by the autonomic nervous system (ANS) remain controversial in both real or simulated microgravity environments for humans or animals. In this study, hindlimb unloading (HU) was used in conscious mice to explore the effects on blood pressure, heart rate, temperature, and locomotor activity. The study found that HU initially induced a decrease in heart rate accompanied by an increase in markers of vagal activity. It also disrupted the day/night rhythmicity of locomotor activity, temperature, and blood pressure.
Article
Anatomy & Morphology
G. Smolyakov, E. Dague, C. Roux, M. H. Seguelas, C. Gales, J. M. Senard, D. N. Arvanitis
BRAIN STRUCTURE & FUNCTION
(2018)