Article
Biochemistry & Molecular Biology
Jens D. Mikkelsen, Sanjay S. Aripaka, Sif Kaad, Burcu A. Pazarlar, Lars Pinborg, Bente Finsen, Andrea Varrone, Benny Bang-Andersen, Jesper F. Bastlund
Summary: A newly developed radioligand [JNJ-64413739] that selectively binds to the purinergic receptor P2X7R has been found to detect neuroinflammation in the brain. The binding properties of JNJ-64413739 in human brain tissue were investigated, and it was found to have different binding abilities in gray and white matter. These findings demonstrate that JNJ-64413739 is suitable for evaluating the distribution and expression of P2X7R in the human brain.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Simona Scheggi, Graziano Pinna, Giulia Braccagni, Maria Graziella De Montis, Carla Gambarana
Summary: Peroxisome proliferator-activator receptors (PPARs) play a role in regulating lipid and glucose metabolism, controlling inflammatory processes, and modulating various brain functions. Among them, PPAR gamma is particularly important in neuropsychiatric and neurodegenerative disorders, with its localization in neuronal circuits involved in emotion modulation and stress response, as well as its role in neurodevelopment and neuroinflammation. Future clinical trials should evaluate the efficacy of PPAR gamma agonists in the treatment of mood and neurodevelopmental disorders such as depression, schizophrenia, and ASD, based on robust preclinical evidence and initial results of clinical studies.
Review
Biochemistry & Molecular Biology
Shinyoung Lee, Hyunsoo Ha, Jaebong Jang, Youngjoo Byun
Summary: The activation of the P2X7 receptor (P2X7R) by elevated levels of extracellular ATP (eATP) in the brain is associated with neuroinflammation, which plays a role in depression. Therefore, targeting P2X7R has become an attractive approach for developing novel antidepressant agents. Several CNS-penetrating P2RX7 antagonists have been developed by multinational pharmaceutical companies and evaluated in clinical trials. This review summarizes the recent progress in the development of P2X7R antagonists for depression treatment.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Frederik J. R. Rombouts, Ken-ichi Kusakabe, Richard Alexander, Nigel Austin, Herman Borghys, Michel De Cleyn, Deborah Dhuyvetter, Harrie J. M. Gijsen, Brian Hrupka, Tom Jacobs, Soufyan Jerhaoui, Lieve Lammens, Laurent Leclercq, Koichi Tsubone, Tatsuhiko Ueno, Kenji Morimoto, Shunsuke Einaru, Hirokazu Sumiyoshi, An Van den Bergh, Ann Vos, Michel Surkyn, Ard Teisman, Diederik Moechars
Summary: A novel class of BACE1 inhibitors with optimized structure and properties was developed in this study, achieving target selectivity and efficacy. By addressing potential toxicity issues through compound optimization, a drug candidate with potential clinical value was obtained.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Anesthesiology
Kazuhiro Hayashi, Joseph B. B. Lesnak, Ashley N. N. Plumb, Lynn A. A. Rasmussen, Kathleen A. A. Sluka
Summary: We developed an animal model of activity-induced muscle pain that relies on the activation of macrophages and the release of interleukin-1 β. The P2X7/NLRP3/Caspase-1 pathway plays a crucial role in the initiation and early maintenance phases of muscle pain in male mice. However, this pathway does not contribute to late maintenance phases in male mice or to muscle pain in female mice.
Article
Biochemistry & Molecular Biology
Ildiko Szabo, Mario Zoratti, Lucia Biasutto
Summary: Targeting mitochondrial ion channels with drugs to eliminate cancer cells is a promising approach due to differential expression and/or regulation of these channels in cancer cells compared to healthy cells. Modulation of ion channels can indirectly affect oxidative phosphorylation, which may be crucial for cancer and cancer stem cell survival. Additionally, modulation of mitochondrial ion channels leading to cytochrome c release may be advantageous in overcoming drug resistance.
Article
Pharmacology & Pharmacy
Germana Cocozza, Stefano Garofalo, Marta Morotti, Giuseppina Chece, Alfonso Grimaldi, Mario Lecce, Ferdinando Scavizzi, Rossella Menghini, Viviana Casagrande, Massimo Federici, Marcello Raspa, Heike Wulff, Cristina Limatola
Summary: In this study, the researchers found that inhibition of K(Ca)3.1 in ALS mouse models can attenuate the pro-inflammatory phenotype of hypothalamic microglia, increase food intake and promote weight gain, as well as change the expression of cannabinoid receptors involved in energy homeostasis. These results highlight a potential new therapeutic target for counteracting weight loss in ALS.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Emma C. Hudgins, Adam M. Bonar, Thanh Nguyen, Ibra S. Fancher
Summary: The dysregulation of lipid-ion channel interactions plays a critical role in the progression of cardiovascular diseases. Blocking these interactions may provide a novel therapeutic approach for preventing disease mechanisms. Lipid regulation of ion channels occurs through direct binding, and preventing these interactions may restore ion channel function and proper control of vascular tone. Potential therapeutic avenues, such as peptides, monoclonal antibodies, and nanomedicine, could be used to prevent pathological lipid-ion channel interactions. However, challenges with experimental identification and development of these strategies need to be addressed.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Immunology
Nolan M. Dvorak, Nadia D. Domingo, Cynthia M. Tapia, Paul A. Wadsworth, Mate Marosi, Yosef Avchalumov, Chanida Fongsaran, Leandra Koff, Jessica Di Re, Catherine M. Sampson, Timothy J. Baumgartner, Pingyuan Wang, Paula P. Villarreal, Olivia D. Solomon, Sonja J. Stutz, Aditi, Jacob Porter, Komi Gbedande, Brendan Prideaux, Thomas A. Green, Erin H. Seeley, Parimal Samir, Kelley T. Dineley, Gracie Vargas, Jia Zhou, Irma Cisneros, Robin Stephens, Fernanda Laezza
Summary: The study investigates the impact of TNF on neuronal excitability in hyperinflammatory cerebral malaria (eCM) and identifies the signaling network involving TNFR1, JAK2, FGF14, and Nav1.6. Plasmodium chabaudi infection increases Nav1.6 channel conductance in CA1 pyramidal neurons through the TNFR1-JAK2-FGF14-Nav1.6 pathway, leading to hyperexcitability. Targeting FGF14 may serve as a potential therapeutic strategy for mitigating TNF-mediated neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Eleonora Grandi, Manuel F. Navedo, Jeffrey J. Saucerman, Donald M. Bers, Nipavan Chiamvimonvat, Rose E. Dixon, Dobromir Dobrev, Ana M. Gomez, Osama F. Harraz, Bence Hegyi, David K. Jones, Trine Krogh-Madsen, Walter Lee Murfee, Matthew A. Nystoriak, Nikki G. Posnack, Crystal M. Ripplinger, Rengasayee Veeraraghavan, Seth Weinberg
Summary: This white paper summarises the outcomes of the seventh UC Davis Cardiovascular Research Symposium on Systems Approach to Understanding Cardiovascular Disease and Arrhythmia. The Symposium aimed to bring together experts in cardiovascular biomedicine to focus on the diversity and signaling involved in cardiovascular function. The paper presents an overview of major cell types, explores the complexity of cardiovascular development and disease at various levels, and discusses technological innovations for advancing understanding of integrated cardiovascular function and dysfunction.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Obstetrics & Gynecology
Noemia A. P. Mariani, Joana Silva, Margarida Fardilha, Erick J. R. Silva
Summary: The high rates of unintended pregnancy and the growing world population pose significant challenges to countries. Expanding male contraceptive options is urgently needed to address these global challenges. Understanding the molecules involved in sperm motility can lead to the development of safe and effective male contraceptives. However, there are challenges in translating preclinical findings into clinical candidates.
HUMAN REPRODUCTION UPDATE
(2023)
Review
Neurosciences
Lu Huang, Guangyin Xu, Ruotian Jiang, Yuncheng Luo, Yunxia Zuo, Jin Liu
Summary: This review summarizes the recent advances and pharmacological properties of two-pore domain potassium (K2P) channels, with a focus on small-molecule activators targeting these channels. The review emphasizes the subtype-selectivity, cellular and in vivo pharmacological properties of various small-molecule activators, and highlights the critical role of K2P channels in pain perception.
CURRENT NEUROPHARMACOLOGY
(2022)
Review
Medicine, General & Internal
Cao Qiang, Zhang Qi, Qiang Yi
Summary: This article reviews the research progress of P2X7 receptors in pain, focusing on their role and mechanism in inflammatory pain, neuropathic pain, cancer pain, and morphine analgesic tolerance. The possible mechanisms of P2X7 receptors involved in pain regulation are also explored through a literature review.
ACTA MEDICA MEDITERRANEA
(2022)
Review
Cell Biology
Raminta Vaiciuleviciute, Daiva Bironaite, Ilona Uzieliene, Ali Mobasheri, Eiva Bernotiene
Summary: OA and CVD share many similarities in terms of risk factors and molecular mechanisms. Many cardiovascular drugs affect cell metabolism, cartilage matrix turnover, and inflammation through ion channels modulation, which may impact joint tissues.
Review
Engineering, Multidisciplinary
Georgina To'a Salazar, Ziyi Huang, Ningyan Zhang, Xue-Guang Zhang, Zhiqiang An
Summary: Analysis of protein families shows membrane-associated GPCRs as dominant drug targets, with challenges in developing specific antibodies due to complexity and uniqueness of amino acid sequences. Addressing these challenges requires design of antigens, antibody generation strategies, lead optimization technologies, and antibody modalities, but approved biologics for targeting complex membrane proteins are limited.
Meeting Abstract
Clinical Neurology
V. Begni, K. C. Creutzberg, F. Marchisella, I. Pisano, M. Papp, M. A. Riva
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Genetics & Heredity
Katarzyna Bialek, Piotr Czarny, Paulina Wigner, Ewelina Synowiec, Gabriela Barszczewska, Michal Bijak, Janusz Szemraj, Monika Niemczyk, Katarzyna Tota-Glowczyk, Mariusz Papp, Tomasz Sliwinski
Summary: Preclinical studies indicate that depression may be triggered by elevated expression of proinflammatory molecules, with key roles in neurochemical, neuroendocrine, and behavioral changes. This study found that chronic mild stress and venlafaxine treatment affect the expression and methylation status of certain inflammatory genes in rats' peripheral blood mononuclear cells and brain structures. Results suggest a partial association between TGFA, TGFB, IRF1, PTGS2, and IKBKB and depressive disorders, with differences observed in antidepressant effects on different brain structures.
Review
Pharmacology & Pharmacy
Mariusz Papp, Wieslaw Jerzy Cubala, Lukasz Swiecicki, Adrian Newman-Tancredi, Paul Willner
Summary: Treatment-resistant depression (TRD) presents a major challenge for mood disorder treatment, but novel treatments like deep brain stimulation and ketamine have shown promise in providing rapid relief for TRD sufferers.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Paola Brivio, Giulia Sbrini, Letizia Tarantini, Chiara Parravicini, Piotr Gruca, Magdalena Lason, Ewa Litwa, Chiara Favero, Marco Andrea Riva, Ivano Eberini, Mariusz Papp, Valentina Bollati, Francesca Calabrese
Summary: Epigenetics plays a crucial role in how environmental factors can affect brain function and contribute to central nervous system disorders. Chronic stress was found to mainly impact the expression and methylation of the Gadd45 beta gene, with lurasidone helping to normalize these alterations. MiRNA involvement in gene expression changes was moderate under the experimental conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Mariusz Papp, Piotr Gruca, Magdalena Lason, Ewa Litwa, Wojciech Solecki, Paul Willner
Summary: The study investigated the synergistic effects of chronic Venlafaxine and repeated optogenetic stimulation on antidepressant non-responsive rats, and found that the combination was effective in restoring normal behavior. While vHPC-mPFC OGS with VEN treatment supported the hypothesis of antidepressant non-responsiveness, dHPC-mPFC OGS alone was effective in improving behavior in the EPM and NOR tests.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Paola Brivio, Erica Buoso, Mirco Masi, Maria Teresa Gallo, Piotr Gruca, Magdalena Lason, Ewa Litwa, Mariusz Papp, Fabio Fumagalli, Marco Racchi, Emanuela Corsini, Francesca Calabrese
Summary: The study focused on the role of the Gr beta-RACK1-Bdnf signaling pathway in susceptibility to chronic stress. Findings showed that activation of this pathway in the ventral hippocampus can increase resilience to chronic stress, offering new targets for treating stress-related disorders.
NEUROBIOLOGY OF STRESS
(2021)
Article
Neurosciences
Mariusz Papp, Piotr Gruca, Magdalena Lason, Ewa Litwa, Wojciech Solecki, Paul Willner
Summary: High frequency optogenetic stimulation of prelimbic cortex can alleviate symptoms of depression in rat models and affect activity in the nucleus accumbens and hippocampus. The stimulation increases the number of Fos-positive cells and active GABAergic cells in these regions.
PSYCHOPHARMACOLOGY
(2022)
Article
Clinical Neurology
V. Begni, I. Pisano, M. Marizzoni, F. Marchisella, K. C. Creutzberg, F. De Rosa, A. Cattaneo, P. Gruca, E. Litwa, M. Papp, M. A. Riva
Summary: This study aimed to investigate the effects of chronic stress and an antipsychotic drug on the response to acute stress in animals. It was found that chronic stress led to reduced sucrose consumption, but lurasidone treatment gradually normalized this change. Additionally, exposure to acute stress resulted in increased Bdnf levels in the prefrontal cortex of control animals, while this response was impaired in animals exposed to chronic stress and restored through lurasidone treatment.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katarzyna Bialek, Piotr Czarny, Paulina Wigner, Ewelina Synowiec, Lukasz Kolodziej, Michal Bijak, Janusz Szemraj, Mariusz Papp, Tomasz Sliwinski
Summary: The study suggests that both chronic mild stress and agomelatine treatment can influence the expression and methylation status of certain genes in both peripheral blood and the brain, indicating their potential association with depression and its treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Paola Brivio, Maria Teresa Gallo, Piotr Gruca, Magdalena Lason, Ewa Litwa, Fabio Fumagalli, Mariusz Papp, Francesca Calabrese
Summary: Stress has a major impact on psychiatric disorders and individuals vary in their susceptibility and response to stress. This study investigated the neural activation and behavioral changes in rats exposed to chronic mild stress (CMS) and subsequently faced with a new acute challenge. The findings suggest that the ventral hippocampus plays a crucial role in both chronic and acute stress response, and targeting this brain region may be a potential therapeutic strategy to enhance stress resilience.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Andrea C. Rossetti, Maria Serena Paladini, Cesar Augusto Bruning, Vittoria Spero, Maria Grazia Cattaneo, Giorgio Racagni, Mariusz Papp, Marco A. Riva, Raffaella Molteni
Summary: Neuroinflammation has been shown to play an important role in the pathophysiology of major depressive disorder (MDD) and the mechanism of action of antidepressants. This study investigated the involvement of IL-6 signaling in the therapeutic effects of the antidepressant drug agomelatine in rats exposed to chronic stress. The results revealed that agomelatine was able to restore the negative modulation of IL-6 signaling and improve the anhedonic-like behavior induced by chronic stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Paola Brivio, Maria Teresa Gallo, Piotr Gruca, Magdalena Lason, Ewa Litwa, Fabio Fumagalli, Mariusz Papp, Francesca Calabrese
Summary: Despite the availability of several antidepressant treatments, they are not effective for all patients. Recently, N-acetylcysteine (NAC) has been explored as a potential adjunctive therapy for psychiatric disorders due to its antioxidant properties. Preclinical studies have shown that NAC can enhance neuroplastic mechanisms and improve resilience, particularly through the modulation of Nr4a1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Neurosciences
Veronica Begni, Moira Marizzoni, Diana Morena Silipo, Kerstin Camile Creutzberg, Mariusz Papp, Annamaria Cattaneo, Marco Andrea Riva
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Laszlo Kiss, Adam Klein, Eric Austin, Dino Dvorak, Silvia Gatti, Mariusz Papp, Gerard Marek, Jonathan Sporn, Zoe Hughes, Andrew Kruegel
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Ilaria Pisano, Veronica Begni, Kerstin Creutzberg, Francesca Marchisella, Federico De Rosa, Mariusz Papp, Annamaria Cattaneo, Marco Andrea Riva
BIOLOGICAL PSYCHIATRY
(2022)