Review
Fisheries
Shuo Li, Tongtong Zhang, Yu Feng, Jinsheng Sun
Summary: Extracellular nucleotides, such as ATP and ADP, released during inflammation or infection, play a crucial role in regulating immune responses in fish by activating specific purinergic receptors on immune cells.
Review
Pharmacology & Pharmacy
Valentina Carotti, Juan P. Rigalli, Jenny van Asbeck-van der Wijst, Joost G. J. Hoenderop
Summary: Purinergic signalling is a process mediated by purinergic receptors, where extracellular nucleotides and nucleosides bind to the receptors, resulting in changes in cell physiology. This signalling is involved in important physiological processes and pathophysiological situations such as cancer and inflammation. Extracellular vesicles (EVs) play a crucial role in modulating purinergic signalling and can affect target cells and tissues located at distant locations. The regulation of extracellular ATP levels and adenosine by EVs has significant impact on processes like inflammation, immune response, and cancer pathogenesis.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Paulo Anastacio Purtado Pacheco, Juliana Vieira Faria, Ana Claudia Silva, Natalia Lidmar von Ranke, Robson Coutinho Silva, Carlos Rangel Rodrigues, David Rodrigues da Rocha, Robson Xavier Faria
Summary: This study evaluated the pharmacological effects of eleven N, S-acetal juglone derivatives as P2x7R inhibitors. Through in vitro and in vivo experiments, we identified one derivative with promising inhibitory activity and low toxicity. Our in silico studies suggest that the 1,4-naphthoquinone moiety might be a valuable molecular scaffold for the development of novel P2x7R antagonists, consistent with our previous research.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Cecilia Astigiano, Francesco Piacente, Maria Elena Laugieri, Andrea Benzi, Christian A. A. Di Buduo, Carolina P. P. Miguel, Debora Soncini, Michele Cea, Antonella Antonelli, Mauro Magnani, Alessandra Balduini, Antonio De Flora, Santina Bruzzone
Summary: SIRT6, a member of the sirtuin family, plays an emerging role in anti-inflammatory processes in various diseases and cell types, including endothelial cells. Overexpression of SIRT6 in human umbilical vein endothelial cells (SIRT6+ HUVECs) was found to affect adhesion molecule levels and promote megakaryocyte proliferation and proplatelet formation. Furthermore, the pro-inflammatory activation of the ATP/purinergic axis was reduced in SIRT6+ HUVECs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Reece Andrew Sophocleous, Lezanne Ooi, Ronald Sluyter
Summary: The article provides an overview of the current understanding of the P2X4 receptor and its role in neuroinflammatory signaling, discussing the pharmacology of P2X4 receptors and targeting molecules, as well as the use of P2X4 receptor modulators and antagonists in neuroinflammatory disease models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ross Luu, Silvana Valdebenito, Eliana Scemes, Antonio Cibelli, David C. Spray, Maximiliano Rovegno, Juan Tichauer, Andrea Cottignies-Calamarte, Arielle Rosenberg, Calude Capron, Sandrine Belouzard, Jean Dubuisson, Djillali Annane, Geoffroy Lorin de la Grandmaison, Elisabeth Cramer-Borde, Morgane Bomsel, Eliseo Eugenin
Summary: The study found that SARS-CoV-2 induces a more significant and prolonged opening of Panx-1 channels compared to other viruses, leading to increased release of ATP, PGE(2), and IL-1 beta. Therefore, the Panx-1 channel is considered a critical factor in SARS-CoV-2 infection and could be a potential alternative therapy.
Review
Pharmacology & Pharmacy
Dominic L. Sykes, Mengru Zhang, Alyn H. Morice
Summary: Chronic cough has been a significant burden for patients, with no approved pharmacological therapies available. However, recent research on the pathophysiological mechanisms of chronic cough has provided new hope, including the potential use of P2X3 receptor antagonists and other emerging peripheral acting pharmacological agents.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Natalia R. Rodriguez, Trinisia Fortune, Thien Vuong, Talia H. Swartz
Summary: Human Immunodeficiency Virus Type 1 (HIV-1) causes a chronic, incurable infection associated with chronic inflammation. Extracellular ATP and P2X receptors play a key role in mediating the chronic inflammation and disease progression in HIV-1 pathogenesis. Future studies should focus on characterizing the functions of ATP and P2X receptors to inform potential therapeutic strategies.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Larissa Berloffa Belardin, Keliane Brochu, Christine Legare, Maria Agustina Battistone, Sylvie Breton
Summary: Purinergic receptors are widely expressed throughout the body and play a role in regulating cell function. They activate specific receptors and trigger different signaling pathways to regulate various cellular responses. Purinergic signaling is important for the physiological and pathophysiological processes in the male reproductive system, but our understanding of this is limited.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Cell Biology
Cora L. Alvarez, Maria F. Troncoso, Maria V. Espelt
Summary: Under nonpathological conditions, extracellular nucleotide concentration remains constant and low, but in cancer, high concentrations of adenine and uridine nucleotides are found in the extracellular space of tumors, acting as extracellular signaling molecules.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Neurosciences
Wen -Jun Zhang, Dong-Xia Hu, Si-Jian Lin, Xiao-Qun Fang, Zhen-Feng Ye
Summary: This article discusses the role of P2X receptors in cerebral ischemic injury and the importance of regulating microglial activity. Activation of P2X receptors has been found to induce inflammatory responses and exacerbate neurological dysfunction, while inhibiting the activation of P2X receptors can help protect nerve function.
BRAIN RESEARCH BULLETIN
(2022)
Article
Agriculture, Dairy & Animal Science
Noemi Gutierrez, Stefanie Teuber, Pablo Alarcon, Rafael A. A. Burgos, Maria A. Hidalgo
Summary: In this study, it was observed that ATP increases inflammatory responses in bovine endometrial cells, such as release of IL-8, intracellular calcium mobilization, and ERK1/2 phosphorylation. The study also discovered the presence of P2Y receptors, specifically high levels of P2Y1 and P2Y2 receptors, in bovine endometrial cells. Inhibition of P2Y receptors reduced the proinflammatory responses induced by ATP. These findings suggest that P2Y receptors play a role in endometrial inflammatory activation and could be a therapeutic target for regulating uterine inflammation.
Review
Pharmacology & Pharmacy
Alexei Verkhratsky
Summary: Purines and pyrimidines are essential molecules for genetic code and bioenergetics. Through evolution, purines have been associated with damage-related extracellular signaling, while plants have developed a sophisticated purinergic signaling system. In vertebrates, the purinergic signaling system operates universally without anatomical or functional segregation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
R. O. Leite, P. O. de Souza, C. B. Haas, F. da Silveira, K. R. Mohr, A. P. S. Bertoni, M. S. Soares, J. H. Azambuja, M. Dal Pra, L. L. P. da Cruz, N. E. Gelsleichter, K. Begnini, G. Hasko, M. R. Wink, R. M. Spanevello, E. Braganhol
Summary: Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. Purinergic signaling, mediated by purines such as ATP and adenosine, plays a crucial role in the immune and inflammatory responses during sepsis. Sepsis disrupts the balance of ATP and adenosine levels, leading to dysregulation of immune responses. The measurement of serum levels and activities of purinergic pathway markers may serve as potential biomarkers for sepsis diagnosis and treatment.
CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Article
Biochemical Research Methods
Alireza Poshtkohi, John Wade, Liam McDaid, Junxiu Liu, Mark Dallas, Angela Bithell
Summary: This research establishes a new mathematical model for investigating P2X-mediated calcium and sodium signaling in human microglial cells. The study reveals that the way P2X receptors regulate ion concentrations is crucial for microglial cell function, providing quantitative insights for future experimental research.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mariasole Perrone, Simone Patergnani, Tommaso Di Mambro, Laura Palumbo, Mariusz R. Wieckowski, Carlotta Giorgi, Paolo Pinton
Summary: Maintenance of mitochondrial quality is crucial for cellular homeostasis. Mitophagy, the selective elimination of dysfunctional mitochondria, plays a significant role in various diseases, including carcinogenesis, neurodegenerative disorders, and cardiovascular pathologies. The relationship between calcium homeostasis and mitophagy is still a topic of debate.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Cell Biology
Simone Patergnani, Antonino Giattino, Nicoletta Bianchi, Carlotta Giorgi, Paolo Pinton, Gianluca Aguiari
Summary: This study reveals that inhibition of mTOR activates autophagy in ADPKD cells, leading to drug degradation through autophagic vesicles and reduced therapeutic efficacy. The combination of mTOR inhibitor and autophagy inhibitor enhances the decrease in cell proliferation caused by mTOR inhibition. Targeting MDM2, a downstream effector of mTOR signaling, prevents TP53 degradation and induces cell apoptosis, providing a new therapeutic option for ADPKD treatment.
BIOLOGY OF THE CELL
(2023)
Article
Biochemistry & Molecular Biology
Sonia Missiroli, Mariasole Perrone, Roberta Gafa, Francesco Nicoli, Massimo Bonora, Giampaolo Morciano, Caterina Boncompagni, Saverio Marchi, Magdalena Lebiedzinska-Arciszewska, Bianca Vezzani, Giovanni Lanza, Franz Kricek, Alessandro Borghi, Francesco Fiorica, Keisuke Ito, Mariusz R. Wieckowski, Francesco Di Virgilio, Luigi Abelli, Paolo Pinton, Carlotta Giorgi
Summary: Uncontrolled inflammatory response from the tumor microenvironment significantly contributes to cancer progression. A trimeric complex at the mitochondria-associated membranes, involving P2X7 receptor-NLRP3 inflammasome interaction, is regulated by the tumor suppressor PML. Downregulation of PML leads to an exacerbated immune response and boosted tumor growth. Mislocalization of PML results in uncontrolled NLRP3 activation and cytokine production, fueling cancer development and worsening prognosis in various human cancers. Mechanistic insights into the PML-P2X7R-NLRP3 axis provide new opportunities for targeted therapeutic approaches in human carcinogenesis.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Developmental Biology
Giovanna Schiuma, Silvia Beltrami, Erica Santi, Gennaro Scutiero, Juana Maria Sanz, Chiara Marina Semprini, Sabrina Rizzo, Mercedes Fernandez, Ines Zidi, Roberta Gafa, Angelina Passaro, Pantaleo Greco, Daria Bortolotti, Roberta Rizzo
Summary: Recent studies have shown differential expression of ACE2 and CD147 in pregnant women with SARS-CoV-2 placental infection. This study aimed to investigate placental SARSCoV-2 infection and its potential effect on protein expression. The results revealed a higher percentage of SARS-CoV-2 NP positive placental samples in the group positive for SARS-CoV-2 at delivery compared to the negative group.
Article
Multidisciplinary Sciences
Valentino Bezzerri, Valentina Gentili, Martina Api, Alessia Finotti, Chiara Papi, Anna Tamanini, Christian Boni, Elena Baldisseri, Debora Olioso, Martina Duca, Erika Tedesco, Sara Leo, Monica Borgatti, Sonia Volpi, Paolo Pinton, Giulio Cabrini, Roberto Gambari, Francesco Blasi, Giuseppe Lippi, Alessandro Rimessi, Roberta Rizzo, Marco Cipolli
Summary: As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. However, current clinical evidence suggests that cystic fibrosis may actually protect against SARS-CoV-2 infection. The expression of SARS-CoV-2 receptors in primary airway epithelial cells is regulated by the CFTR channel, and dysfunctional CFTR channels in cystic fibrosis cells result in reduced viral entry and replication.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Biochemistry & Molecular Biology
Francesco Di Virgilio, Valentina Vultaggio-Poma, Simonetta Falzoni, Anna Lisa Giuliani
Summary: The discovery of the P2X7 receptor in immune cells raised hopes for the development of anti-inflammatory drugs, but initial clinical trials were disappointing, reducing industry interest in P2X7-targeted therapies. However, recent findings have revitalized the use of P2X7 in diagnostic medicine, with new radioligands proving reliable for neuroinflammation diagnosis and P2X7 measurement in blood suggesting its potential as an inflammation marker. This review provides an overview of these novel developments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Valentina Albanese, Sonia Missiroli, Mariasole Perrone, Martina Fabbri, Caterina Boncompagni, Salvatore Pacifico, Tiziano De Ventura, Antonella Ciancetta, Giulio Dondio, Franz Kricek, Paolo Pinton, Remo Guerrini, Delia Preti, Carlotta Giorgi
Summary: A series of aryl sulfonamide derivatives (ASDs) were designed and synthesized to inhibit the activation of the NLRP3 inflammasome. Compounds 6c, 7n, and 10 specifically inhibited NLRP3 activation at nanomolar concentrations without affecting the activation of other inflammasomes. These compounds were also found to reduce IL-1 beta production in vivo and attenuate melanoma tumor growth. The findings suggest that these potent NLRP3 inflammasome inhibitors could be considered for future therapeutic approaches in NLRP3 inflammasome-driven cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Nutrition & Dietetics
Domenico Sergi, Juana Maria Sanz, Stefano Lazzer, Gloria Brombo, Giovanni Zuliani, Gianni Biolo, Bostjan Simunic, Rado Pisot, Edoardo Dalla Nora, Angelina Passaro
Summary: Dietary lipids play a crucial role in modulating metabolic inflammation, and interleukin 18 (IL-18) has been consistently linked to obesity and insulin resistance. This study aimed to assess if the quality of lipid intake affects IL-18 plasma levels and its implications on insulin resistance. The study confirmed that IL-18 is positively correlated with insulin resistance, and individuals with higher HOMA-IR levels displayed elevated IL-18 levels. The quality of dietary lipids, particularly the ratio between different fatty acids and the intake of omega-3, showed a negative correlation with IL-18 levels.
Article
Multidisciplinary Sciences
Juana Maria Sanz, Andrea D'Amuri, Domenico Sergi, Sharon Angelini, Valeria Fortunato, Elda Favari, Giovanni Vigna, Giovanni Zuliani, Edoardo Dalla Nora, Angelina Passaro
Summary: Familial Hypercholesterolemia (FH) is associated with high LDL cholesterol and premature cardiovascular disease. This study aimed to investigate the impact of FH on cholesterol efflux capacity (CEC) and its relationship with lipoprotein subfraction distribution. The results showed that FH patients had higher concentrations of all LDL subfractions, a shift towards small HDL subfractions, and increased CEC compared to controls.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Valentina Vultaggio-Poma, Juana Maria Sanz, Andrea Amico, Alessandra Violi, Sara Ghisellini, Stefano Pizzicotti, Angelina Passaro, Alberto Papi, Marco Libanore, Francesco Di Virgilio, Anna Lisa Giuliani
Summary: This study found that the levels of sP2X7R in the blood of patients with COVID-19 were increased and correlated with adverse clinical outcomes. sP2X7R may be a useful marker of disease progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Salvatore Greco, Juana Maria Sanz, Daria Bortolotti, Chiara Marina Semprini, Carlotta Braga, Roberta Gafa, Erica Santi, Iva Maestri, Roberta Rizzo, Pantaleo Greco, Angelina Passaro
Summary: This study reports a case of a newborn who died from pulmonary embolism and superior vena cava thrombosis caused by SARS-CoV-2 infection. Autopsy findings showed positive SARS-CoV-2 N-protein and Spike RBD in multiple tissues, suggesting potential intrauterine transmission.
FRONTIERS IN MEDICINE
(2023)
Article
Cell Biology
Nada Dhaouadi, Veronica Angela Maria Vitto, Paolo Pinton, Lorenzo Galluzzi, Saverio Marchi
Summary: Multiple forms of regulated cell death (RCD) are associated with the activation of specific molecular mechanisms. Ca2+ ions can physically interact and regulate various components of the RCD machinery, leading to organellar dysfunction and increased sensitivity to cell death induced by other stressors.
Review
Cell Biology
Gokhan Burcin Kubat, Esmaa Bouhamida, Oner Ulger, Ibrahim Turkel, Gaia Pedriali, Daniela Ramaccini, Ozgur Ekinci, Berkay Ozerklig, Ozbeyen Atalay, Simone Patergnani, Beyza Nur Sahin, Giampaolo Morciano, Meltem Tuncer, Elena Tremoli, Paolo Pinton
Summary: Skeletal muscle is a dynamic and plastic tissue that plays a vital role in movement, posture, and force production. It functions as an endocrine organ capable of producing and secreting bioactive molecules. Various pathological conditions can disrupt the balance between muscle protein synthesis and degradation, leading to skeletal muscle atrophy.
