Article
Pharmacology & Pharmacy
Nathaniel A. K. Glenn, David B. Finlay, Emma R. Carruthers, Kathleen G. Mountjoy, Christopher S. Walker, Natasha L. Grimsey
Summary: The interactions between RAMPs and MRAPs with GPCRs play a significant role in modulating the expression and signaling of these receptors, particularly in cannabinoid receptors CB1, CB2, GPR18, and GPR55. The binding of CB1, CB2, and GPR55 with MRAPs influences their surface expression, possibly through glycosylation and hetero-oligomerization mechanisms, which potentially leads to physiological and disease-related consequences.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Orkun Cevheroglu, Nil Demir, Mehmet Seckin Kesici, Salih Ozcubukcu, Cagdas D. Son
Summary: GPR56 is an adhesion GPCR that regulates neural progenitor cell migration in the brain and inhibits cell migration in glioma cells. This receptor couples with various G proteins and signals through different downstream pathways. The study found that BFPP mutants disrupting GPR56 function showed distinct defects in signalling for each G protein and different activation mechanisms for beta-arrestin involvement.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matthias Apweiler, Jana Streyczek, Soraya Wilke Saliba, Juan Antonio Collado, Thomas Hurrle, Simone Graessle, Eduardo Munoz, Claus Normann, Sabine Hellwig, Stefan Braese, Bernd L. Fiebich
Summary: Anti-neuroinflammatory treatment is important in the search for pharmacological treatments of neurological and psychiatric diseases. Clinical studies have shown a reduction in symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivatives have anti-neuroinflammatory effects and may have reduced side-effects compared to known drugs. This study evaluated the anti-inflammatory capacities of two coumarin-based compounds in human cells and mouse microglia, and found varying effects on different parameters, possibly due to functional selectivity and tissue or cell-dependent expression of GPR55.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Monica Patel, David B. Finlay, Michelle Glass
Summary: SCRAs were originally developed to explore therapeutic benefits of cannabinoid receptor activation, but have been diverted to the recreational drug market, potentially leading to toxicity. Biased agonists can maximize drug effectiveness by reducing adverse effects, but the signaling pathways of cannabinoid receptors are still unclear.
CELLULAR SIGNALLING
(2021)
Article
Pharmacology & Pharmacy
Michaela Dvorakova, Agnieszka Kubik-Zahorodna, Alex Straiker, Radislav Sedlacek, Alena Hajkova, Ken Mackie, Jaroslav Blahos
Summary: SGIP1 interacts with CB1 receptors and may modulate affect, anxiety, pain processing, and other physiological processes. SGIP1(-/-) mice show decreased anxiety-like behaviors and increased sensitivity to nociception/analgesics in behavioral tests.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Review
Neurosciences
Jamie J. Manning, Hayley M. Green, Michelle Glass, David B. Finlay
Summary: The CB1 receptor is a promising drug target for a wide range of diseases, but existing ligands have limited therapeutic potential. Recent drug development efforts have focused on altering CB1 signaling by modulating endocannabinoid signaling or selectively targeting specific cellular pathways.
Article
Biochemistry & Molecular Biology
Shane C. Wright, Michel Bouvier
Summary: GPCRs continue to be a focus in drug discovery efforts due to their widespread expression and broad role in signal transduction. Despite over 800 GPCRs sharing a common architecture, unique differences govern ligand specificity and pathway selectivity. Recent biosensor development has reinforced the idea that biased signaling may become mainstream in drug discovery programs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Oncology
Tamara T. T. Lah, Bernarda Majc, Metka Novak, Ajda Susnik, Barbara Breznik, Andrej Porcnik, Roman Bosnjak, Aleksander Sadikov, Marta Malavolta, Selma Halilcevic, Jernej Mlakar, Roby Zomer
Summary: In glioblastoma, the upregulation of GPR55 and TRPV1 receptors is correlated with GBM stem cell gene markers, making them potential targets for eliminating GBM stem cells. The mixture of CBG and CBD shows high cytotoxicity and should be further studied for its therapeutic potential in animal experiments and clinical trials.
Editorial Material
Neurosciences
Arnau Busquets-Garcia, Miriam Melis, Luigi Bellocchio, Giovanni Marsicano
Summary: This article introduces the wide expression and regulatory functions of the endocannabinoid system in both the brain and the periphery. It discusses the distribution of cannabinoid receptors in different cell types and compartments, and highlights the different cellular or molecular effects mediated by these receptors. The article also mentions the expression of the endocannabinoid system throughout the body and its role in modulating the connection between the brain and the periphery. Lastly, it emphasizes the importance of understanding the cannabinoid receptors structure and pharmacology for the development of novel allosteric modulators.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Thangesweran Ayakannu, Anthony H. Taylor, Justin C. Konje
Summary: The expression of GPR55 was found to be significantly higher in patients with endometrial cancer compared to control tissues. GPR55 levels were correlated with its transcript levels and inversely correlated with CB2 receptor protein expression, suggesting a potential role for GPR55 as a biomarker and therapeutic target in endometrial cancer.
HISTOCHEMISTRY AND CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yanli Qiu, Yitian Zhao, Tao Hu, Meifang Yang, Fei Li, Cuixia Li, Weiliang Gu, Xiaodi Yang, Suwen Zhao, Houchao Tao
Summary: In this study, a new Yin-Yang ligand with antagonist activity on CB1 and agonist activity on CB2 was developed. By modifying the N1-phenyl group in the pyrazole-cored scaffold, various ligands with distinct activities were obtained. Molecular docking and molecular dynamic simulation revealed that the desired Yin-Yang bifunctionality was a result of hydrogen bonding with S173 and S285 in CB1 and CB2, respectively. This study demonstrates the feasibility of structure-guided ligand evolution for challenging Yin-Yang ligands.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mikhail G. Akimov, Natalia M. Gretskaya, Polina V. Dudina, Galina D. Sherstyanykh, Galina N. Zinchenko, Oksana V. Serova, Ksenia O. Degtyaryova, Igor E. Deyev, Vladimir V. Bezuglov
Summary: GPR55 is an atypical cannabinoid receptor that plays an important role in cancer cell proliferation. Depending on the ligand, it can either promote cell proliferation or cell death. This study used the CRISPR-Cas9 system to knockout the GPR55, CB1, CB2, and GPR18 receptors in the MDA-MB-231 cell line. The results showed that the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor disappeared after the CB2 receptor knockout, indicating a signaling pathway between these two receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Plant Sciences
John T. Hancock, Grace Russell
Summary: Molecular hydrogen (H2) is considered part of the small molecules that can control cellular activity, potentially used in human disease therapy and plant growth enhancement. Its molecular action is still unclear, but it may act through antioxidative effects or by influencing cell antioxidation capacity, with possible interactions with heme oxygenase activity or reactive nitrogen species. However, there is controversy surrounding the suggested mechanisms, with downstream mechanisms still needing critical review.
Article
Developmental Biology
Farah Saad, David R. Hipfner
Summary: The Hedgehog (Hh) pathway is regulated by G protein-coupled receptors (GPCRs) in Drosophila, with Mthl5 identified as a modulator of this pathway. This suggests potential crosstalk between GPCRs and the Hh pathway in mammals as well.
Article
Multidisciplinary Sciences
Mohamed Mahameed, Pengli Wang, Shuai Xue, Martin Fussenegger
Summary: In this study, synthetic receptors targeted to the secretory pathway were engineered with orientation adjustment of receptor parts and elimination of dysfunctional post-translational modification sites. These receptors exhibited diverse locations in the cytoplasm, endoplasmic reticulum, or on the plasma membrane.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Mariangela Pucci, Elizabeta Zaplatic, Maria Vittoria Micioni Di Bonaventura, Emanuela Micioni Di Bonaventura, Paolo De Cristofaro, Mauro Maccarrone, Carlo Cifani, Claudio D'Addario
Summary: Different neuromodulatory systems, particularly the endocannabinoid system, are involved in long-term energy balance and body weight regulation. Further investigation on the transcriptional regulation of the gene encoding type-1 cannabinoid receptors is essential in understanding the development of obesity and eating disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Emanuele Criscuolo, Maria Laura De Sciscio, Filomena Fezza, Mauro Maccarrone
Summary: Research suggests that the therapeutic efficacy of compounds targeted towards FAAH should be tested in vitro on both rat and human enzymes.
Review
Urology & Nephrology
Mauro Maccarrone, Cinzia Rapino, Felice Francavilla, Arcangelo Barbonetti
Summary: Cannabinoids and endocannabinoids can affect various aspects of human male reproduction. Preclinical studies have shown that the endocannabinoid system is involved in negative modulation of testosterone secretion, but the effect of cannabinoids on spermatogenesis remains a matter of debate. A better understanding of the complex crosstalk between cannabinoids and endocannabinoids may enable targeting the ECS for modulation of human fertility.
NATURE REVIEWS UROLOGY
(2021)
Review
Cell Biology
Lucia Scipioni, Francesca Ciaramellano, Veronica Carnicelli, Alessandro Leuti, Anna Rita Lizzi, Noemi De Dominicis, Sergio Oddi, Mauro Maccarrone
Summary: This article reviews the role of microglial cells in chronic inflammation in Alzheimer's disease (AD) and the involvement of endocannabinoids in regulating their activity.
Article
Biochemistry & Molecular Biology
Luca Navarini, Marta Vomero, Stefano Di Donato, Damiano Currado, Onorina Berardicurti, Annalisa Marino, Pietro Bearzi, Alice Biaggi, Matteo Ferrito, Piero Ruscitti, Marina Fava, Alessandro Leuti, Paola Cipriani, Mauro Maccarrone, Roberto Giacomelli
Summary: This study found that 2-AG modulates the production of type 2 interferon in CD4+ T lymphocytes from SLE patients through CB2 activation.
Article
Biochemistry & Molecular Biology
Daniel Tortolani, Camilla Di Meo, Sara Standoli, Francesca Ciaramellano, Salam Kadhim, Eric Hsu, Cinzia Rapino, Mauro Maccarrone
Summary: Rare cannabis-derived phytocannabinoids (pCBs) have therapeutic potential in skin disorders and their anti-inflammatory effects were investigated in this study. The experiment involved using lipopolysaccharide (LPS) to induce inflammation in human keratinocytes (HaCaT cells) and measuring the levels of pro-inflammatory interleukins. The results showed that pCBs significantly reduced the release of pro-inflammatory interleukins and modulated MAPK signaling, suggesting their potential as a treatment for inflammation-related skin pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Francesca Liberatore, Nico Antenucci, Daniel Tortolani, Giada Mascio, Federico Fanti, Manuel Sergi, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti, Mauro Maccarrone, Serena Notartomaso
Summary: Research has shown that using mGlu1 receptor PAM can partially correct learning deficits in SCA1 mouse models, restore memory retention, and increase levels of endocannabinoid anandamide in the hippocampus.
Article
Biochemistry & Molecular Biology
Sara Standoli, Cinzia Rapino, Camilla Di Meo, Agnes Rudowski, Nicole Kaempfer-Kolb, Luisa Michelle Volk, Dominique Thomas, Sandra Trautmann, Yannick Schreiber, Dagmar Meyer zu Heringdorf, Mauro Maccarrone
Summary: Microglia, the immune cells of the central nervous system, have important roles in brain homeostasis and various neurological diseases. This study investigates the interaction between the endocannabinoid system and the sphingosine kinase/sphingosine-1-phosphate system in microglia. The results reveal that inhibiting the fatty acid amide hydrolase enzyme and activating the cannabinoid 2 receptor have anti-inflammatory effects and prevent the transcription of pro-inflammatory SphK1 and SphK2 in microglia cells challenged with lipopolysaccharide. The findings suggest the development of inhibitors for these enzymes as potential treatments for neuroinflammatory diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Annamaria Tisi, Giulia Carozza, Alessandro Leuti, Rita Maccarone, Mauro Maccarrone
Summary: The study investigates the alterations of RvE1 metabolism and signaling in an animal model of age-related macular degeneration (AMD), and suggests a potentially relevant role of this pathway in AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Gianna Rossi, Valentina Di Nisio, Alessandro Chiominto, Sandra Cecconi, Mauro Maccarrone
Summary: This study aimed to investigate the expression levels of the main receptors and metabolic enzymes of the endocannabinoid system in the ovaries, oviducts, and uteri of mice at different reproductive stages. The results showed that TRPV1 receptor had the highest expression and significantly increased during aging, while NAPE-PLD, FAAH, and DAGL-beta enzymes were the most expressed in these organs and increased with age. Immunohistochemistry revealed the distribution of these proteins in specific cells in each organ. These findings provide new insights into the role of the endocannabinoid system in female reproduction and its therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mauro Maccarrone
Summary: Lipids, traditionally known for their role as metabolic fuel and structural membrane components, have been found to act as authentic messengers between cells and regulate various biological processes in the body. This article focuses on endogenous bioactive lipids, particularly those derived from arachidonic acid (AA), and their interactions with other lipids, enzymes, and receptors. The metabolic and signal transduction pathways of classical eicosanoids, endocannabinoids, specialized pro-resolving mediators, and other bioactive lipids such as shingosine-1-phosphate and steroid hormones will be discussed.
Review
Pharmacology & Pharmacy
Mauro Maccarrone, Vincenzo Di Marzo, Jurg Gertsch, Uwe Grether, Allyn C. Howlett, Tian Hua, Alexandros Makriyannis, Daniele Piomelli, Natsuo Ueda, Mario van der Stelt
Summary: Marijuana, a widely used recreational drug, has seen a change in risk perception due to its legalization and medical use. Research has shown the therapeutic potential of cannabinoids for various diseases, and our body's endocannabinoid system plays a crucial role in this. Understanding the components and functions of this system can lead to new treatment opportunities.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Cell Biology
Giulia Leanza, Caterina Conte, Francesca Cannata, Camilla Isgro, Alessandra Piccoli, Rocky Strollo, Carlo Cosimo Quattrocchi, Rocco Papalia, Vincenzo Denaro, Mauro Maccarrone, Nicola Napoli, Anna Maria Sardanelli
Summary: In this study, the oxidative stress states were compared between postmenopausal women with and without obesity. The results showed that women with obesity had doubled levels of oxidative stress markers compared to women of normal weight. The severity of oxidative stress was correlated with body mass index, visceral fat mass, and trunk fat percentage, but not with fasting glucose levels. These findings suggest that obesity and visceral fat increase oxidative stress in postmenopausal women, potentially increasing the risks of cardiometabolic and cancer diseases.
Review
Biochemistry & Molecular Biology
Annamaria Tisi, Sakthimala Palaniappan, Mauro Maccarrone
Summary: This article presents the application of advanced omics techniques, such as genomics, transcriptomics, and epigenomics, in cochlear research. The article also introduces the latest technologies, including single-cell omics and spatial omics, for investigating molecular events at a single-cell resolution with spatial information.
Article
Neurosciences
Michela Bossa, Ornella Argento, Chiara Piacentini, Nicola Manocchio, Lucia Scipioni, Sergio Oddi, Mauro Maccarrone, Ugo Nocentini
Summary: This project aims to evaluate the anti-neuroinflammatory effects of oral administration of N-palmitoylethanolamine (PEA) in subjects with mild cognitive impairment (MCI) through cognitive evaluation and biochemical analyses. The specific objectives are to determine whether PEA can affect neuropsychological and behavioral scores, change inflammatory and neuronal damage markers in MCI subjects, and if these changes correlate with clinical scores.