Review
Biochemistry & Molecular Biology
Almudena Robledo-Menendez, Maria Vella, Pedro Grandes, Edgar Soria-Gomez
Summary: Hippocampal circuits play a crucial role in cognitive performance and are deeply affected in pathological conditions. Cannabinoid receptors regulate different cell types within hippocampal circuitries. Understanding the precise mechanisms triggered by cannabinoid receptor activation at a cellular and subcellular level helps in grasping hippocampal pathophysiological states.
Review
Neurosciences
P. H. Gobira, S. R. Joca, F. A. Moreira
Summary: Addiction to psychostimulant drugs is a significant public health issue and cannabinoid receptors CB1R and CB2R play a crucial role in modulating the rewarding effects of these drugs. This review summarizes studies on pharmacological intervention targeting CB1R and CB2R and their interaction in psychostimulant responses.
ACTA NEUROPSYCHIATRICA
(2022)
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)
Review
Biochemistry & Molecular Biology
Kangtai Xu, Yifei Wu, Zhuangzhuang Tian, Yuanfan Xu, Chaoran Wu, Zilong Wang
Summary: Pain, especially chronic pain, has a significant impact on patients' quality of life. Cannabinoids have shown potent analgesic effects in preclinical pain models by acting as agonists of CB1 and CB2 receptors. While the activation of CB1 receptors is associated with psychotropic adverse effects, the promising target for pain treatment is the CB2 receptors primarily expressed in immune cells. Microglia, as resident immune cells in the central nervous system, play a critical role in chronic pain, and CB2 receptors regulate their activity and function. This review focuses on the role of microglial CB2 receptors in spinal nociceptive circuitry and their implications for selective CB2 receptor agonist-mediated analgesia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Battistina Asproni, Gabriele Murineddu, Paola Corona, Gerard A. Pinna
Summary: Cannabinoids are a class of compounds with different pharmacological properties. Their affinity towards CB1 and/or CB2 receptors has led to the synthesis of tricyclic pyrazole-based compounds with high affinity and selectivity, showing potential in the treatment of neuropathic pain, obesity, or glaucoma management.
Article
Biochemistry & Molecular Biology
George Amato, Vineetha Vasukuttan, Danni Harris, Lucas Laudermilk, Jennifer Lucitti, Scott Runyon, Rangan Maitra
Summary: Partial agonists targeting peripheral cannabinoid receptors have potential therapeutic applications in various medical conditions. In this study, a novel compound that is a partial agonist of the human CB1 receptor with reduced brain exposure was identified.
Article
Chemistry, Medicinal
Daniela R. de Oliveira, Rodolfo C. Maia, Patricia R. de Carvalho Franca, Patricia D. Fernandes, Gisele Barbosa, Lidia M. Lima, Carlos A. Manssour Fraga
Summary: This study investigates the potential mechanism of action of dipyrone and proposes the modulation of cannabinoid receptors CB1 and CB2 as a promising hypothesis. A series of novel pyrazolamides were designed and synthesized with good physicochemical properties and stability. These compounds demonstrated inverse agonist characteristics on CB2 receptors and showed remarkable analgesic activity in a mouse model, suggesting their potential for treating pain syndromes associated with chronic inflammatory diseases.
Article
Immunology
Clare Brown, Matthew Mitsch, Karis Blankenship, Carly Campbell, Mimi Pelanne, Jaylan Sears, Abigail Bell, Alicia K. Olivier, Matthew K. Ross, Todd Archer, Barbara L. F. Kaplan
Summary: With the growing popularity of marijuana and CBD in humans, there is increasing interest in using cannabinoids in veterinary medicine. Studies have shown that cannabis-containing extracts may be beneficial for dogs with inflammatory diseases, and there is interest in their immunosuppressive potential for immune-mediated diseases in dogs. Further research is needed to understand the mechanisms and effects of cannabinoids in dogs.
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
(2023)
Article
Neurosciences
Philippe De Deurwaerdere, Maurizio Casarrubea, Daniel Cassar, Manuela Radic, Emilie Puginier, Abdeslam Chagraoui, Giuseppe Crescimanno, Vincenzo Crunelli, Giuseppe Di Giovanni
Summary: Childhood absence epilepsy is often accompanied by neuropsychological comorbidities such as anxiety. This study found that the synthetic cannabinoid receptor agonist WIN 55,212-2 had strain-dependent effects on anxiety-like and motor behavior in rats with absence epilepsy. The study also revealed alterations in cerebral monoaminergic levels in these rats, suggesting a role of endocannabinoids and monoamines in the comorbidities.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Bashir Bietar, Sophie Tanner, Christian Lehmann
Summary: The endocannabinoid system offers a promising avenue for therapeutic interventions, but the presence of cannabinoid receptors in various organs and tissues can complicate targeted treatments. Injuries to the central nervous system can induce neuroinflammation and potentially affect the immune system. Exploring immunomodulatory therapies provides a hopeful alternative in the face of challenges in traditional preventive treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Barbara Vuic, Tina Milos, Lucija Tudor, Marcela Konjevod, Matea Nikolac Perkovic, Maja Jazvinscak Jembrek, Gordana Nedic Erjavec, Dubravka Svob Strac
Summary: Neurodegenerative diseases, characterized by protein aggregation in the brain, can be influenced by the activation of CB2 receptors in the endocannabinoid system. Studies suggest that activating CB2 receptors has potential benefits in reducing protein aggregation-based pathology, attenuating inflammation, and alleviating dementia-related symptoms.
Article
Pharmacology & Pharmacy
Luis Gustavo A. Patrone, Gustavo D. D. Ferrari, Rodrigo Moreira da Silva, Luciane C. C. Alberici, Norberto Peporine Lopes, Angelita M. M. Stabile, Wilfried Klein, Kenia C. Bicego, Luciane H. H. Gargaglioni
Summary: Cannabis legalization has led to increased cannabis use during pregnancy. This study found that prenatal exposure to synthetic cannabinoid WIN can affect the respiratory control system of neonatal and juvenile rats, with greater CO2 sensitivity in males and breathing and brainstem changes. In females, it leads to increased apnea and reduced serotonin neurons. These findings demonstrate long-term and sex-specific consequences of excessive stimulation of the endocannabinoid system during gestation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Neurosciences
Mengya Wang, Huayuan Liu, Zegang Ma
Summary: Parkinson's disease is a neurodegenerative disease influenced by the cannabinoid system in the basal ganglia. Modulating the endogenous cannabinoid levels can have an anti-movement disorder effect, suggesting the development of drugs targeting the cannabinoid system as a novel strategy for Parkinson's disease treatment.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Immunology
Arailym Sarsembayeva, Melanie Kienzl, Eva Gruden, Dusica Ristic, Kathrin Maitz, Paulina Valadez-Cosmes, Ana Santiso, Carina Hasenoehrl, Luka Brcic, Joerg Lindenmann, Julia Kargl, Rudolf Schicho
Summary: Cannabinoid (CB) receptors, particularly CB2, play an important role in the tumor microenvironment of non-small cell lung cancer (NSCLC). Deficiency of CB2 reduces tumor burden and enhances the activity of immune cells, leading to improved response to anti-PD-1 therapy. CB2 could be a potential adjuvant target for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Veterinary Sciences
Roberto Chiocchetti, Riccardo Rinnovati, Claudio Tagliavia, Agnese Stanzani, Giorgia Galiazzo, Fiorella Giancola, Margherita De Silva, Ylenia Capodanno, Alessandro Spadari
Summary: This study aimed to localize the cellular distribution of canonical and putative cannabinoid receptors in the equine cervical dorsal root ganglia. Through immunohistochemical methods, it was found that neurons showed immunoreactivity for CB1R, CB2R, PPAR alpha, TRPA1, and 5-HT1aR, while neuronal satellite glial cells showed immunoreactivity for CB2R, PPAR alpha, TRPA1, and 5-HT1aR. The study highlighted the expression of cannabinoid receptors in the sensory neurons and glial cells of the dorsal root ganglia.
EQUINE VETERINARY JOURNAL
(2021)
Article
Medicine, Research & Experimental
Tanja Grossmann, Barbara Steffan, Andrijana Kirsch, Magdalena Grill, Claus Gerstenberger, Markus Gugatschka
Summary: This study investigated the isolated or combined effects of cigarette smoke extract and vibration on human vocal fold fibroblasts in an in vitro setting, revealing their influence on the pathophysiology of Reinke's edema. Some genes and proteins in the context of RE were only significantly affected when CSE in combination with vibration was applied.
Article
Pharmacology & Pharmacy
Eva Knuplez, Melanie Kienzl, Athina Trakaki, Rudolf Schicho, Akos Heinemann, Eva M. Sturm, Gunther Marsche
Summary: Miltefosine has a strong modulatory activity in regulating eosinophilic inflammation both in vitro and in vivo, showing potential efficacy in treating allergic diseases and other eosinophil-associated disorders. This may lead to important questions regarding the immunomodulatory effect of miltefosine in patients treated for leishmania infections.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Mahmoud Abdellatif, Viktoria Trummer-Herbst, Franziska Koser, Sylvere Durand, Rui Adao, Francisco Vasques-Novoa, Johanna K. Freundt, Julia Voglhuber, Maria-Rosaria Pricolo, Michael Kasa, Clara Turk, Fanny Aprahamian, Elias Herrero-Galan, Sebastian J. Hofer, Tobias Pendl, Lavinia Rech, Julia Kargl, Nathaly Anto-Michel, Senka Ljubojevic-Holzer, Julia Schipke, Christina Brandenberger, Martina Auer, Renate Schreiber, Chintan N. Koyani, Akos Heinemann, Andreas Zirlik, Albrecht Schmidt, Dirk von Lewinski, Daniel Scherr, Peter P. Rainer, Julia von Maltzahn, Christian Muhlfeld, Marcus Kruger, Sasa Frank, Frank Madeo, Tobias Eisenberg, Andreas Prokesch, Adelino F. Leite-Moreira, Andre P. Lourenco, Jorge Alegre-Cebollada, Stefan Kiechl, Wolfgang A. Linke, Guido Kroemer, Simon Sedej
Summary: The study suggests that using nicotinamide to increase NAD(+) can improve cardiac dysfunction in HFpEF patients by enhancing myocardial energy metabolism and directly improving cardiomyocyte function. High intake of naturally occurring NAD(+) precursors is associated with lower blood pressure and reduced risk of cardiac mortality.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Dominika Kovacs, Viola Bagone Vantus, Eszter Vamos, Nikoletta Kalman, Rudolf Schicho, Ferenc Gallyas, Balazs Radnai
Summary: The study showed that the PARP inhibitor olaparib improved experimental Crohn's disease by reducing inflammation, enhancing barrier integrity, and regulating cytokine levels. In both the TNBS-induced mouse colitis model and Caco-2 monolayer culture, olaparib demonstrated anti-inflammatory and protective effects on the epithelial barrier.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Article
Immunology
Paulina Valadez-Cosmes, Kathrin Maitz, Oliver Kindler, Sofia Raftopoulou, Melanie Kienzl, Ana Santiso, Zala Nikita Mihalic, Luka Brcic, Jorg Lindenmann, Melanie Fediuk, Martin Pichler, Rudolf Schicho, A. McGarry Houghton, Akos Heinemann, Julia Kargl
Summary: Neutrophils in cancer patients, specifically LDNs, are found to have pro-tumor properties compared to HDNs. New surface markers have been identified to distinguish between LDNs and HDNs in NSCLC patients, providing potential diagnostic and prognostic tools for tumor progression clarification.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Magdalena Grill, Isaac Lazzeri, Andrijana Kirsch, Nina Steurer, Tanja Grossmann, Michael Karbiener, Ellen Heitzer, Markus Gugatschka
Summary: Reinke's edema is a voice disorder associated with smoking and voice abuse, characterized by changes in vocal fold fibroblasts. Differential expression analysis between RE and control VFF revealed upregulated genes and pathways involved in extracellular matrix remodeling, inflammation, and fibrosis, while downregulated genes and pathways were associated with ECM degradation, cell cycle control, and proliferation.
Article
Biochemistry & Molecular Biology
Sofia Raftopoulou, Paulina Valadez-Cosmes, Zala Nikita Mihalic, Rudolf Schicho, Julia Kargl
Summary: Neutrophils play crucial roles in cancer progression, being regulated by tumor microenvironment factors during their release, recruitment, and functional polarization processes. Moreover, neutrophils actively stimulate the tumor microenvironment through secreted factors that affect immune interactions and subsequent tumor progression. Understanding different neutrophil subpopulations or polarization states, as well as identifying tumor microenvironment-derived factors of neutrophil polarization, would allow us to fully harness the potential of neutrophils as complementary targets in anticancer precision therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Taylor E. Syme, Magdalena Grill, Emina Hayashida, Barney Viengkhou, Iain L. Campbell, Markus J. Hofer
Summary: This study demonstrates that SBNO2 acts as a novel negative feedback regulator of IL-6 in the brain, restraining its excessive inflammatory actions and providing protection against neuroinflammation and neurodegeneration.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Gunther Marsche, Julia T. Stadler, Julia Kargl, Michael Holzer
Summary: Atherosclerosis is a disease characterized by increased oxidative stress, leading to modifications of proteins and lipids in the blood vessel wall. Myeloperoxidase (MPO), an enzyme mainly found in neutrophils and monocytes, plays a crucial role in this oxidative process. Research has shown that MPO interacts with lesion derived high-density lipoprotein (HDL) and modifies its components, leading to dysfunction of HDL. Understanding the impact of MPO-induced changes on the structure and function of HDL is important for the future use of HDL in diagnostics and therapy.
Article
Biochemistry & Molecular Biology
Katharina B. Kuentzel, Ivan Bradic, Zala N. Mihalic, Melanie Korbelius, Silvia Rainer, Anita Pirchheim, Julia Kargl, Dagmar Kratky
Summary: Advanced maternal age and obesity are the main risk factors for gestational diabetes mellitus (GDM). In this study, we investigated the dysregulation of intracellular lipases in pregnancies complicated by maternal high-fat/high-cholesterol (HF/HCD) feeding with and without GDM. The results suggest that dysregulation of placental lipid hydrolysis may contribute to fetal hepatic lipid accumulation and fetal overgrowth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Tanja Grossmann, Andrijana Kirsch, Magdalena Grill, Barbara Steffan, Michael Karbiener, Luka Brcic, Barbara Darnhofer, Ruth Birner-Gruenberger, Markus Gugatschka
Summary: Research on human vocal fold biology is limited due to the sensitive microstructure of the vocal fold mucosa. We developed an alternative model using human buccal epithelial cells and vocal fold fibroblasts, which closely resembles native vocal fold mucosa in terms of histology and proteomics. This model provides a reproducible in vitro platform for various research opportunities.
Article
Biochemistry & Molecular Biology
Julia T. Stadler, Hansjoerg Habisch, Florian Prueller, Harald Mangge, Thomas Baernthaler, Julia Kargl, Anja Pammer, Michael Holzer, Sabine Meissl, Alankrita Rani, Tobias Madl, Gunther Marsche
Summary: This study compares the lipoprotein and metabolic profiles of COVID-19-infected patients and non-COVID-19 pneumonia patients, and finds significant differences in HDL-related parameters between the two groups. The cholesterol efflux capacity (CEC) shows the strongest negative association with COVID-19 mortality.
Article
Medicine, Research & Experimental
Huajia Zhang, Xiaodong Zhu, Travis J. Friesen, Jeff W. Kwak, Tatyana Pisarenko, Surapat Mekvanich, Mark A. Velasco, Timothy W. Randolph, Julia Kargl, A. McGarry Houghton
Summary: This study reveals the expression of ARG1 in neutrophil lineage cells in non-small cell lung cancer and the active transcription of ARG7 mRNA in tumor-associated neutrophils (TANs). ANXA2 is identified as the major driver of ARG7 mRNA expression in TANs through signaling via the TLR2/MYD88 axis. This study uncovers a novel mechanism in regulating ARG7 mRNA expression in neutrophils and emphasizes the crucial role of neutrophil lineage cells in suppressing tumor-infiltrating lymphocytes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Melanie Kienzl, Carina Hasenoehrl, Kathrin Maitz, Arailym Sarsembayeva, Ulrike Taschler, Paulina Valadez-Cosmes, Oliver Kindler, Dusica Ristic, Sofia Raftopoulou, Ana Santiso, Thomas Baernthaler, Luka Brcic, Lisa Hahnefeld, Robert Gurke, Dominique Thomas, Gerd Geisslinger, Julia Kargl, Rudolf Schicho
Summary: The MGL expressed in the tumor microenvironment plays a crucial role in promoting tumor growth in NSCLC, as shown by experiments with MGL inhibitor and MGL knock-out mice. Inhibition of MGL results in decreased tumor burden, accompanied by increased numbers of CD8(+) T cells and eosinophils, indicating enhanced tumoricidal activity.
Article
Biochemistry & Molecular Biology
Gabriel Chalhoub, Stephanie Kolleritsch, Lisa K. Maresch, Ulrike Taschler, Laura Pajed, Anna Tilp, Helgit Eisner, Philipp Rosina, Benedikt Kien, Franz P. W. Radner, Rudolf Schicho, Monika Oberer, Gabriele Schoiswohl, Guenter Haemmerle
Summary: Research showed that CES2/Ces2 members are highly efficient DG and MG hydrolases, potentially playing an important role in liver and gut lipid signaling. In addition to TG hydrolysis, Ces2a, Ces2b, and Ces2e exhibited significant enzymatic activities towards DGs and MGs.
JOURNAL OF LIPID RESEARCH
(2021)