Article
Pharmacology & Pharmacy
Nedjma Labani, Florence Gbahou, Marc Noblet, Bernard Masri, Olivier Broussaud, Jianfeng Liu, Ralf Jockers
Summary: This study examined the effects of 25 commercial plant extracts on cellular assays and found that Ex18, an extract from Pistacia vera dried fruits, had potent effects on melatonin receptor expressing cells. The extract was found to have high levels of endogenous melatonin and contained additional active principles that enhanced the effects of melatonin. These findings may have therapeutic potential.
Review
Pharmacology & Pharmacy
Rafael Franco, Gemma Navarro
Summary: G protein-coupled receptors (GPCRs) are the targets of many approved drugs, and it is now recognized that they form heteromers with each other. This review discusses strategies for selectively targeting GPCRs in heteromeric contexts, such as exploiting biased signaling, developing drugs with higher affinity for heteromer-associated receptors, using allosteric compounds, and blocking both receptors in a heteromer. Heteromers provide unique allosteric sites that could be targeted for the development of heteromer-selective drugs. The review also highlights the potential of targeting GPCRs in heteromers for neuroprotection, delaying disease progression, and addressing complications of Parkinson's disease therapy.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Romain Gerbier, Delphine Ndiaye-Lobry, Pablo B. Martinez de Morentin, Erika Cecon, Lora K. Heisler, Philippe Delagrange, Florence Gbahou, Ralf Jockers
Summary: Functional fingerprint of heteromers composed of G(i)-coupled melatonin MT2 receptors and G(q)-coupled serotonin 5-HT2C receptors was identified in mouse brain, with melatonin activating G(q) proteins and PLC in a concentration-dependent manner in the hypothalamus and cerebellum. These effects were absent in cortex, inhibited by the 5-HT2C receptor-specific inverse agonist SB-243213, and were fully recapitulated in MT2 and 5-HT2C knockout mice. Furthermore, antidepressant agomelatine had similar effects to melatonin but blocked melatonin-promoted G(q) activation due to its 5-HT2C antagonistic component, providing strong functional evidence for the existence of MT2/5-HT2C heteromeric complexes.
Article
Neurosciences
Nana Gao, Wei Zheng, Tiliwaerde Murezati, Wei Gu, Xiaorong Li, Zengliang Jin
Summary: The study suggests that GW117 functions as a serotonin 2C (5-HT2C) receptor antagonist and melatonin type 1 and 2 (MT1/MT2) receptor agonist, showing evident antidepressant and anxiolytic effects.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Review
Cell Biology
Preeti Kumari Chaudhary, Soochong Kim
Summary: GPCRs play a crucial role in cancer progression, but the specific mechanisms of their involvement are still unclear. Studies have revealed the multifaceted impact of GPCRs on cancer development and the signaling pathways involved.
Article
Multidisciplinary Sciences
Jingyi Zhao, Vincent DiGiacomo, Mariola Ferreras-Gutierrez, Shiva Dastjerdi, Alain Ibanez de Opakua, Jong-Chan Park, Alex Luebbers, Qingyan Chen, Aaron Beeler, Francisco J. Blanco, Mikel Garcia-Marcos
Summary: IGGi-11 selectively inhibits noncanonical activation of heterotrimeric G-protein signaling, blocking tumor cell signaling and inhibiting metastatic cancer cell invasion without interfering with canonical GPCR signaling mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Alexander S. Hauser, Charlotte Avet, Claire Normand, Arturo Mancini, Asuka Inoue, Michel Bouvier, David E. Gloriam
Summary: Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors coupled to G proteins, but there are differences in the reported G protein couplings among recent large-scale datasets. This study presents a common coupling map that uncovers novel couplings, GPCR-G protein selectivity, and the comparison of co-coupling and co-expression of G proteins with phylogenetic relationships. These findings will advance receptor research and cellular signaling, and contribute to the development of safer drugs.
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Mireia Casanovas, Irene Reyes-Resina, Alejandro Lillo, Jaume Lillo, Raul Lopez-Arnau, Jorge Camarasa, Elena Escubedo, Gemma Navarro, Rafael Franco
Summary: The study found that methamphetamine affects the function of A(2A) and CB1 receptors, blocking the activation of the MAPK pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Haichang Luo, Ezequiel Marron Fernandez de Velasco, Kevin Wickman
Summary: G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels play a critical inhibitory role in neurons. They are regulated by G proteins, phosphatidylinositol 4,5-bisphosphate (PIP2), phosphorylation, regulator of G protein signaling (RGS) proteins, as well as intracellular Na+ and Ca2+. Various stimuli can modify neuronal GIRK channel activity transiently or persistently, including exposure to drugs of abuse, changes in neuronal activity patterns, and aversive experience. Dysregulation of GIRK channel activity has been implicated in neurological diseases and disorders.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Physiology
Davide Calebiro, Zsombor Koszegi, Yann Lanoiselee, Tamara Miljus, Shannon O'Brien
Summary: Recent research has revealed transient interactions between GPCRs and G proteins in living cells, resulting in short-lived signaling nanodomains that may confer rapidity and specificity to signal transduction. These findings could potentially offer new strategies for modulating GPCR function and pave the way for innovative drug development for common diseases like diabetes or heart failure.
PHYSIOLOGICAL REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Alexander P. Young, Eileen M. Denovan-Wright
Summary: This article discusses the roles of microglia in the development and resolution of neuroinflammation. It highlights the potential therapeutic target of the endocannabinoid system for chronic neuroinflammation and suggests that activation of cannabinoid type 2 receptors may be responsible for its anti-inflammatory effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jin Hee Kim, In Gyoung Ju, Namkwon Kim, Eugene Huh, So-Ri Son, Joon Pyo Hong, Yujin Choi, Dae Sik Jang, Myung Sook Oh
Summary: This study aimed to investigate the anti-neuroinflammatory effects of yomogin, isolated from Artemisia iwayomogi. The results showed that yomogin suppressed neuroinflammatory factors and regulated the MAPK pathway, suggesting its potential as a therapeutic candidate for inflammation-mediated neurological diseases.
Article
Cell Biology
Jong Min Hong, Jin-Woo Lee, Dong-Seung Seen, Jae-Yeon Jeong, Won-Ki Huh
Summary: The heteromerization between CXCR4 and LPA1 has been investigated, showing its important role in cancer cells and providing insights into the regulatory mechanism of CXCR4 through heteromer formation. The findings suggest a potential therapeutic approach using combined CXCR4 and LPA1 inhibitors for cancer and inflammatory diseases associated with these receptors.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Plant Sciences
Zahra Ayatollahi, Vaiva Kazanaviciute, Volodymyr Shubchynskyy, Kotryna Kvederaviciute, Manfred Schwanninger, Wilfried Rozhon, Michael Stumpe, Felix Mauch, Sebastian Bartels, Roman Ulm, Salma Balazadeh, Bernd Mueller-Roeber, Irute Meskiene, Alois Schweighofer
Summary: This study reveals the crucial role of different types of MAPK phosphatases in plant stress responses and the tight control of MAPK activities.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Pathology
Marco Montella, Stefano Luca, Andrea Ronchi, Federica Zito Marino, Alessandro Caputo, Antonello Sica, Pio Zeppa, Renato Franco, Immacolata Cozzolino
Summary: This article reports a series of 12 cases of anaplastic large cell lymphoma (ALCL) diagnosed by cytology. The results show that the cytological diagnosis of ALCL can be challenging, and rapid on-site evaluation, cell block preparation, immunocytochemistry, and molecular assessment are necessary for accurate diagnosis and differential diagnosis. When samples are properly managed, cytology can provide a reliable final diagnosis of ALCL.
Review
Biochemistry & Molecular Biology
Rafael Franco, Joan Serrano-Marin
Summary: The tricarboxylic acid (TCA) cycle, also known as the Krebs cycle, is essential for energy production and anabolic processes in cells. While not as tightly regulated as other key metabolic pathways, it plays a crucial role in understanding and addressing diseases related to mitochondrial dysfunction. This article suggests the need for better understanding and regulation of TCA cycle enzyme activity, including the possible direct regulation by G protein-coupled receptors (GPCRs) in mitochondrial membranes.
Article
Cell Biology
Rafael Rivas-Santisteban, Iu Raich, David Aguinaga, Carlos A. Saura, Rafael Franco, Gemma Navarro
Summary: The study discovered a direct interaction between PrPC and NMDAR, which alters the functionality of the receptor. Significant overexpression of NMDAR-PrPC complexes was observed in the AD model, and PrPC exacerbates the axonal transport of Tau and pTau proteins.
Article
Pathology
Andrea Ronchi, Marco Montella, Emma Carraturo, Eduardo Clery, Federica Zito Marino, Martina Amato, Giuseppe Argenziano, Elvira Moscarella, Gabriella Brancaccio, Teresa Troiani, Pasquale Alfano, Roberto Alfano, Renato Franco, Immacolata Cozzolino
Summary: BRAF molecular evaluation on cell suspension obtained from FNAC needle rinses is a time-saving and accurate technique for diagnostic and predictive purpose in the clinical practice.
Letter
Psychiatry
Rafael Franco, Eva Martinez-Pinilla
Summary: Theobromine consumption in cocoa/chocolate is associated with an increased risk of depression, according to a recent article in BMC Psychiatry. However, it is challenging to establish a correlation between dietary habits and depression risk, as the diagnosis of depression is complex. Additionally, assessing the amount of theobromine is not easy due to variations in chocolate brands and cocoa percentage. Alternatively, it is speculated that individuals with depression may benefit from consuming products containing theobromine. Further research could explore the correlation between theobromine intake and the type of therapy used in depressed individuals, as some antidepressant drugs affect cravings for sweet products.
Article
Oncology
Stefano Luca, Renato Franco, Antonella Napolitano, Valeria Soria, Andrea Ronchi, Federica Zito Marino, Carminia Maria Della Corte, Floriana Morgillo, Alfonso Fiorelli, Antonio Luciano, Giuseppe Palma, Claudio Arra, Sabrina Battista, Laura Cerchia, Monica Fedele
Summary: Lung cancer, especially non-small cell lung cancer (NSCLC), has a high mortality rate and lacks effective therapies. Immunotherapy shows promise, but predicting success is challenging. This study investigated the relationship between PATZ1 and PD-L1 expression in NSCLC and found that they are negatively associated. PATZ1 overexpression downregulates PD-L1 expression and inhibits NSCLC cell proliferation, migration, and invasion, suggesting it may act as a tumor suppressor in NSCLC.
Article
Medicine, General & Internal
Giuseppa Zannini, Ilaria Tedesco, Immacolata Cozzolino, Marco Montella, Eduardo Clery, Carminia Maria Della Corte, Floriana Morgillo, Marina Accardo, Renato Franco, Federica Zito Marino
Summary: This study aimed to evaluate the quantity and quality of nucleic acids extracted from mixed stained slides (MSSs) compared to unstained slides (USs). It was found that DNA extracted from MSSs showed satisfactory results while RNA extraction was not successful.
Article
Chemistry, Medicinal
Claudia Llinas del Torrent, Iu Raich, Angel Gonzalez, Nil Casajuana-Martin, Jaume Lillo, Joan Biel Rebassa, Carlos Ferreiro-Vera, Veronica Saanchez de Medina, Rafael Franco, Gemma Navarro, Leonardo Pardo
Summary: The amino acid at position 6.51 plays a key role in the initial mechanism of activation of G-protein coupled receptors (GPCRs) that recognize signaling molecules derived from lipid species. This study provides insights into the binding and activation abilities of THC and the agonist JWH-133 on CB1 and CB2 receptors.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Cell Biology
Alejandro Lillo, Joan Serrano-Marin, Jaume Lillo, Iu Raich, Gemma Navarro, Rafael Franco
Summary: Microglial activation is often seen in patients with neurodegenerative diseases. A study investigated the effect of adenosine receptor ligands on microglial activation and identified potential biomarkers associated with immune system-related events.
Review
Biochemistry & Molecular Biology
Rafael Franco, Joan Serrano-Marin, Gemma Navarro, Rafael Rivas-Santisteban
Summary: This review discusses the potential role of the renin angiotensin system (RAS) in the central nervous system, particularly in the treatment of Parkinson's disease. The expression of RAS in dopaminergic neurons may impact dopamine synthesis and oxidative stress detoxification, and the regulation of glucose-6-phosphate dehydrogenase activity may involve the activation of protein kinase A and/or protein kinase C.
Article
Biochemistry & Molecular Biology
Niklas Rosier, Denise Moennich, Martin Nagl, Hannes Schihada, Alexei Sirbu, Nergis Konar, Irene Reyes-Resina, Gemma Navarro, Rafael Franco, Peter Kolb, Paolo Annibale, Steffen Pockes
Summary: Dopamine D-1-like receptors are the most abundant type of dopamine receptors in the central nervous system. The synthesis of new fluorescent ligands derived from D1R antagonist SCH-23390 was described, which can be used as tools for the visualization of D-1-like receptors. The high-affinity ligand UR-NR435 (25) showed excellent selectivity towards D-1-like receptors and proved to be a neutral antagonist in binding studies. This fluorescent ligand is a useful tool for studying native D-1 receptors in various experimental setups.
Article
Biochemistry & Molecular Biology
Martin Nagl, Denise Moennich, Niklas Rosier, Hannes Schihada, Alexei Sirbu, Nergis Konar, Irene Reyes-Resina, Gemma Navarro, Rafael Franco, Peter Kolb, Paolo Annibale, Steffen Pockes
Summary: This study describes the synthesis of a set of new fluorescent ligands for visualization of dopamine D-2-like receptors. The ligand UR-MN212 (20) showed high affinity for D-2-like receptors and moderate selectivity towards D-1-like receptors. It displayed rapid association with D2longR and can be used for fluorescence microscopy studies. The ligand's binding affinity was determined in a single-digit nanomolar range, consistent with radioligand binding data.