Article
Immunology
Irene Santos-Garcia, Carmen Rodriguez-Cueto, Patricia Villegas, Fabiana Piscitelli, Anna Lauritano, Che-Kun J. Shen, Vincenzo Di Marzo, Javier Fernandez-Ruiz, Eva de Lago
Summary: This study used a mouse model of frontotemporal dementia (FTD) and found that increasing endocannabinoid levels can improve the neuropathology caused by FTD, reduce glial reactivity, protect neuronal integrity, and improve cognitive, emotional, and social deficits.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Pharmacology & Pharmacy
Anugrah D. Santoso, Dirk De Ridder
Summary: Modulation of FAAH has immense potential as a new therapeutic candidate for several disorders, but further exploration is still needed to determine the best treatment strategy.
CANNABIS AND CANNABINOID RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Adriana Della Pietra, Juha Savinainen, Rashid Giniatullin
Summary: This thematic review discusses the potential use of inhibiting endocannabinoid-degrading enzymes to increase endocannabinoid levels and alleviate migraine pain. It also explores the migraine pain signaling pathways, the complex effects of endocannabinoids in pain modulation, and emerging inhibitors to target these pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Tugce Gur Maz, Sumeyye Turanli, H. Burak Caliskan, Burcu Caliskan, Erden Banoglu
Summary: A series of novel piperazine urea derivatives with thiadiazole moieties were designed, synthesized, and investigated for their inhibition potential against human fatty acid amide hydrolase (hFAAH). The urea derivatives possessing p-chlorophenylthiadiazole and benzylpiperazine fragments were identified as effective inhibitors of hFAAH, with compounds containing 4-chlorobenzyl and 4-fluorobenzyl tails showing the highest activity.
ARCHIV DER PHARMAZIE
(2022)
Review
Biochemistry & Molecular Biology
Ana Lago-Fernandez, Sara Zarzo-Arias, Nadine Jagerovic, Paula Morales
Summary: Cannabinoids exert therapeutic effects through various targets including cannabinoid receptors and nuclear receptors. Simultaneous targeting of CBRs and PPAR alpha or PPAR gamma subtypes has shown to mediate diverse properties of cannabinoids for specific disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Justin Matheson, Xin Ming Matthew Zhou, Zoe Bourgault, Bernard Le Foll
Summary: Research suggests that modulating enzymes involved in the synthesis and degradation of endocannabinoids, such as FAAH, MAGL, and DAGL, may be an effective strategy for treating obesity. In animal models, inhibiting FAAH tends to promote obesity, while genetic deletion of Mgll and Dagla, as well as pharmacological inhibition of DAGL, tends to reduce body weight and improve metabolic state. The effects of Mgll manipulation, however, are tissue-dependent and require further investigation.
Article
Biochemistry & Molecular Biology
Sanela Rajlic, Luise Surmann, Pia Zimmermann, Christina Katharina Weisheit, Laura Bindila, Hendrik Treede, Markus Velten, Andreas Daiber, Georg Daniel Duerr
Summary: Ischemic cardiomyopathy leads to inflammation and left ventricular dysfunction. Animal studies suggest that the endocannabinoid system may have cardioprotective effects, including cardiomyocyte adaptation, inflammation, and remodeling. This study investigates the potential cardioprotective effect of the endocannabinoid anandamide (AEA) after ischemia and reperfusion using FAAH (-/-) mice and suggests that increased endocannabinoids may have detrimental effects on cardiomyocyte survival due to PPAR-alpha activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Melissa Simard, Anne-Sophie Archambault, Jean-Philippe C. Lavoie, Elizabeth Dumais, Vincenzo Di Marzo, Nicolas Flamand
Summary: This review discusses the biosynthesis and metabolism of endocannabinoids 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA), as well as their congeners, with a special focus on the metabolism by oxygenases involved in arachidonic acid metabolism. The authors highlight the knowledge gaps in our understanding of the regulation and roles of the oxyendocannabinoidome mediators.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Daniele Piomelli, Alex Mabou Tagne
Summary: Endocannabinoids are lipid-derived messengers that regulate various physiological processes in mammals. Dysfunctions in their activity have been linked to diseases, leading to interest in the endocannabinoid system as a potential source of therapeutic drugs. This review provides an overview of endocannabinoid formation, deactivation, and biotransformation, and discusses the properties and therapeutic potential of pharmacological agents that interfere with these processes.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2022)
Article
Biochemical Research Methods
Reshed Abohalaka, Turgut Emrah Bozkurt, Tuba Recber, Sevgen Celik Onder, Emirhan Nemutlu, Sedef Kir, Inci Sahin-Erdemli
Summary: The endocannabinoid system plays a crucial role in respiratory diseases, and modulation of endocannabinoid levels can prevent airway inflammation and hyperreactivity. Treatment with FAAH or MAGL inhibitors locally or systemically did not cause significant histopathological changes in mice, but had a significant impact on the levels of endocannabinoid metabolites in the lungs.
BIOMEDICAL CHROMATOGRAPHY
(2022)
Review
Biochemistry & Molecular Biology
Leila Hosseinzadeh Anvar, Ali Ahmadalipour
Summary: This review focuses on the associations between the FAAH C385A polymorphism and various diseases or traits. Although there is variability in the results, the overall consensus is that the FAAH C385A genotype may affect susceptibility to some multifactorial disorders and could be considered a potential therapeutic target.
Article
Biochemistry & Molecular Biology
Shreya Dharadhar, Willem J. van Dijk, Serge Scheffers, Alexander Fish, Titia K. Sixma
Summary: This study uncovers the crucial regulatory role of insert L1 in USP1 activity during DNA replication, highlighting its importance for both substrate-mediated activity enhancement and allosteric activation upon UAF1 binding.
Article
Clinical Neurology
Jennifer Spohrs, Martin Ulrich, Georg Groen, Paul L. Plener, Birgit Abler
Summary: The study found that the FAAH C385A allele can influence brain neural activation and modulate extinction memory recall. Furthermore, the endocannabinoid system, particularly AEA, plays a modulatory role in the extinction of aversive memory.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Greta Niemela, Garth E. Terry
Summary: Recent research suggests that chronic alcohol exposure induces changes in the endocannabinoid system, making it a potential target for understanding and treating AUD. Studies focused on the role of FAAH, an enzyme that degrades anandamide, in the biology of AUD and found that FAAH modulation may impact alcohol consumption and withdrawal symptoms. Inhibition of FAAH shows promise for reducing withdrawal symptoms but may also lead to increased alcohol preference and intake, indicating the need for further research.
CANNABIS AND CANNABINOID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Alessandro Deplano, Jessica Karlsson, Federica Moraca, Mona Svensson, Claudia Cristiano, Carmine Marco Morgillo, Christopher J. Fowler, Roberto Russo, Bruno Catalanotti, Valentina Onnis
Summary: The study identifies Flu-AM4 as a dual-action FAAH/substrate-selective COX inhibitor with anti-inflammatory and analgesic activity in animal pain models.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Beatrice Dufrusine, Silvia Valentinuzzi, Sandra Bibbo, Verena Damiani, Paola Lanuti, Damiana Pieragostino, Piero Del Boccio, Ersilia D'Alessandro, Alberto Rabottini, Alessandro Berghella, Nerino Allocati, Katia Falasca, Claudio Ucciferri, Francesco Mucedola, Marco Di Perna, Laura Martino, Jacopo Vecchiet, Vincenzo De Laurenzi, Enrico Dainese
Summary: This study identified significant changes in proteins involved in iron metabolism in COVID-19 patients and long-COVID patients. The activation of 5-LOX was also observed, possibly through an iron-dependent mechanism. Leukotriene B4 and lipocalin 2 were suggested as potential markers for COVID-19 and long-COVID.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Biochemistry & Molecular Biology
Michele Sallese, Konstantinos Efthymakis, Michele Marchioni, Benedetto Neri, Beatrice Dufrusine, Enrico Dainese, Marta Di Nicola, Matteo Neri
Summary: Coeliac disease (CeD) is an immune-mediated disorder triggered by gluten, involving autoimmune damage to the intestines and other systems. The Th1 inflammatory response and innate immune response play important roles in its pathogenesis. Gene expression analysis found key cytokines and immune pathways involved. Comparison with non-celiac gluten sensitivity (NCGS) revealed molecular overlap, suggesting a common root (dysregulated long non-coding RNAs) for these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Oncology
Beatrice Dufrusine, Emily Capone, Sara Ponziani, Rossano Lattanzio, Paola Lanuti, Francesco Giansanti, Vincenzo De Laurenzi, Stefano Iacobelli, Rodolfo Ippoliti, Annunziato Mangiola, Gianluca Trevisi, Gianluca Sala
Summary: This study demonstrates that vesicular galectin-3-binding protein (LGALS3BP) is a potential diagnostic biomarker and therapeutic target for glioblastoma multiforme (GBM). Immunohistochemical analysis shows high expression of LGALS3BP in GBM patient tissues, and the amount of vesicular LGALS3BP is increased compared to healthy donors. Furthermore, analysis of extracellular vesicles from mice with human GBM indicates that LGALS3BP can be used as a marker for liquid biopsy. An antibody-drug conjugate (ADC) targeting LGALS3BP, named 1959-sss/DM4, shows specific accumulation in tumor tissue and produces potent antitumor activity. Overall, this work provides evidence for the importance of LGALS3BP as a diagnostic biomarker and therapeutic target for GBM, warranting further validation in preclinical and clinical studies.
MOLECULAR ONCOLOGY
(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.
Article
Biotechnology & Applied Microbiology
Giorgia Perpetuini, Alessio Pio Rossetti, Lucia Giordano, Marta Pulcini, Beatrice Dufrusine, Noemi Battistelli, Camillo Zulli, Giuseppe Arfelli, Alberto Palliotti, Enrico Dainese, Rosanna Tofalo
Summary: The aim of this study was to characterize the ampelographic and genetic profiles of Vitis vinifera L. cv. Nero Antico di Pretalucente and to describe the grape-borne fungal communities. The study also investigated the oenological characteristics and aroma profile of wine obtained by spontaneous fermentation. Results showed that this cultivar presented a unique profile, indicating that it is a distinct and autochthonous grape variety.
FERMENTATION-BASEL
(2023)
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
Multidisciplinary Sciences
Valeria Di Lollo, Angelo Canciello, Alessia Peserico, Massimiliano Orsini, Valentina Russo, Adrian Cervero-Varona, Beatrice Dufrusine, Mohammad El Khatib, Valentina Curini, Annunziata Mauro, Paolo Berardinelli, Cathy Tournier, Massimo Ancora, Cesare Camma, Enrico Dainese, Luana Fiorella Mincarelli, Barbara Barboni
Summary: This study reveals the impact of epithelial-mesenchymal transition (EMT) on the immune properties of amniotic epithelial cells (AECs). The response to lipopolysaccharide differs between pre-EMT (eAECs) and post-EMT (mAECs), with eAECs upregulating genes involved in antigen-presenting response and mAECs over-expressing soluble inflammatory mediator transcripts. Network analysis identifies CIITA and Nrf2 as the main drivers of eAECs and mAECs immune response, respectively.