332 results match your criteria ligands circadian


Novel Insight of Histamine and Its Receptor Ligands in Glaucoma and Retina Neuroprotection.

Biomolecules 2021 08 11;11(8). Epub 2021 Aug 11.

Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Pharmacology and Toxicology Section, University of Florence, 50139 Florence, Italy.

Glaucoma is a multifactorial neuropathy characterized by increased intraocular pressure (IOP), and it is the second leading cause of blindness worldwide after cataracts. Glaucoma combines a group of optic neuropathies characterized by the progressive degeneration of retinal ganglionic cells (RGCs). Increased IOP and short-term IOP fluctuation are two of the most critical risk factors in glaucoma progression. Read More

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DPP acutely defines the connectivity of central pacemaker neurons in .

J Neurosci 2021 Aug 24. Epub 2021 Aug 24.

Laboratorio de Genética del Comportamiento. Fundación Instituto Leloir. IIB-BA CONICET. Buenos Aires, Argentina.

Rhythmic rest-activity cycles are controlled by an endogenous clock. In , this clock resides in ∼150 neurons organized in clusters whose hierarchy changes in response to environmental conditions. The concerted activity of the circadian network is necessary for the adaptive responses to synchronizing environmental stimuli. Read More

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RORγ is a context-specific master regulator of cholesterol biosynthesis and an emerging therapeutic target in cancer and autoimmune diseases.

Biochem Pharmacol 2021 Aug 9:114725. Epub 2021 Aug 9.

Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, CA, USA; UC Davis Comprehensive Cancer Center, University of California, Davis, Sacramento, CA, USA; VA Northern California Health Care System, Mather, CA, USA. Electronic address:

Aberrant cholesterol metabolism and homeostasis in the form of elevated cholesterol biosynthesis and dysregulated efflux and metabolism is well recognized as a major feature of metabolic reprogramming in solid tumors. Recent studies have emphasized on major drivers and regulators such as Myc, mutant p53, SREBP2, LXRs and oncogenic signaling pathways that play crucial roles in tumor cholesterol metabolic reprogramming. Therapeutics such as statins targeting the mevalonate pathway were tried at the clinic without showing consistent benefits to cancer patients. Read More

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Probing the Microduplication Linkage to Schizophrenia in Animal and Cellular Models.

Front Neurosci 2021 22;15:717490. Epub 2021 Jul 22.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Pituitary adenylate cyclase-activating polypeptide (PACAP, gene name ) is a multifunctional neuropeptide involved in brain development and synaptic plasticity. With respect to PACAP function, most attention has been given to that mediated by its specific receptor PAC1 (). However, PACAP also binds tightly to the high affinity receptors for vasoactive intestinal peptide (VIP, ), called VPAC1 and VPAC2 ( and , respectively). Read More

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Melatonin and the circadian system: Keys for health with a focus on sleep.

Handb Clin Neurol 2021 ;179:331-343

Institute of Cellular and Integrative Neurosciences, CNRS, University of Strasbourg, Strasbourg, France.

Melatonin (MLT), secreted during the night by the pineal gland, is an efferent hormonal signal of the master circadian clock located in the suprachiasmatic nucleus (SCN). Consequently, it is a reliable phase marker of the SCN clock. If one defines as "chronobiotic," a drug able to influence the phase and/or the period of the circadian clock, MLT is a very potent one. Read More

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Circadian clock genes as promising therapeutic targets for autoimmune diseases.

Autoimmun Rev 2021 Aug 10;20(8):102866. Epub 2021 Jun 10.

Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address:

Circadian rhythm is a natural, endogenous process whose physiological functions are controlled by a set of clock genes. Disturbance of the clock genes have detrimental effects on both innate and adaptive immunity, which significantly enhance pro-inflammatory responses and susceptibility to autoimmune diseases via strictly controlling the individual cellular components of the immune system that initiate and perpetuate the inflammation pathways. Autoimmune diseases, especially rheumatoid arthritis (RA), often exhibit substantial circadian oscillations, and circadian rhythm is involved in the onset and progression of autoimmune diseases. Read More

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The Microbiota and the Gut-Brain Axis in Controlling Food Intake and Energy Homeostasis.

Int J Mol Sci 2021 May 29;22(11). Epub 2021 May 29.

Microbial Ecology, Nutrition & Health Research Unit, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), 46980 Valencia, Spain.

Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Read More

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Circadian control of hepatitis B virus replication.

Nat Commun 2021 03 12;12(1):1658. Epub 2021 Mar 12.

Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease and cancer worldwide for which there are no curative therapies. The major challenge in curing infection is eradicating or silencing the covalent closed circular DNA (cccDNA) form of the viral genome. The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the liver transcriptome and yet their role in HBV replication is unknown. Read More

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Bile acids and their receptors in metabolic disorders.

Prog Lipid Res 2021 04 23;82:101094. Epub 2021 Feb 23.

Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy.

Bile acids are a large family of atypical steroids which exert their functions by binding to a family of ubiquitous cell membrane and nuclear receptors. There are two main bile acid activated receptors, FXR and GPBAR1, that are exclusively activated by bile acids, while other receptors CAR, LXRs, PXR, RORγT, S1PR2and VDR are activated by bile acids in addition to other more selective endogenous ligands. In the intestine, activation of FXR and GPBAR1 promotes the release of FGF15/19 and GLP1 which integrate their signaling with direct effects exerted by theother receptors in target tissues. Read More

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Space-time logic of liver gene expression at sub-lobular scale.

Nat Metab 2021 01 11;3(1):43-58. Epub 2021 Jan 11.

Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

The mammalian liver is a central hub for systemic metabolic homeostasis. Liver tissue is spatially structured, with hepatocytes operating in repeating lobules, and sub-lobule zones performing distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. Read More

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January 2021

Clock Genes, Inflammation and the Immune System-Implications for Diabetes, Obesity and Neurodegenerative Diseases.

Int J Mol Sci 2020 Dec 21;21(24). Epub 2020 Dec 21.

Laboratory of Cardiovascular and Dysmetabolic diseases, IRCCS MultiMedica, 20138 Milan, Italy.

Inflammation is a common feature of several diseases, including obesity, diabetes and neurodegenerative disorders. Circadian clock genes are expressed and oscillate in many cell types such as macrophages, neurons and pancreatic β cells. During inflammation, these endogenous clocks control the temporal gating of cytokine production, the antioxidant response, chemokine attraction and insulin secretion, among other processes. Read More

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December 2020

The Possible Role of Endozepines in Sleep Regulation and Biomarker of Process S of the Borbély Sleep Model.

Chronobiol Int 2021 01 13;38(1):122-128. Epub 2020 Dec 13.

The Research Institute of Applied Chronobiology, Tel-Hai Academic College , Upper Galilee, Israel.

The well-known Two-Process Model of Sleep Regulation describes the integration of the circadian rhythm of arousal and sleep - Process C, and the homeostatic pressure to sleep - Process S. Presently, the known biological markers for Process C are melatonin and core body temperature; whereas, for Process S, there is no biological marker except that of aspects of the electroencephalogram (EEG). Endozepines are a class of endogenous compounds that act like benzodiazepines (BZ), i. Read More

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January 2021

Corticosteroids and circadian rhythms in the cardiovascular system.

Curr Opin Pharmacol 2021 04 15;57:21-27. Epub 2020 Nov 15.

Cardiovascular Endocrinology Laboratory, Baker Heart & Diabetes Institute, Melbourne, VIC, Australia; Cardiovascular Endocrinology Laboratory, Hudson Institute of Medical Research, Clayton, VIC, Australia; Department of Molecular & Translational Science, Monash University, Clayton, VIC, Australia; Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia. Electronic address:

The mineralocorticoid receptor (MR) plays a central role in cardiac physiological function and disease and is thus an attractive therapeutic target for patients with heart failure. However, the incidence of significant side effects from mineralocorticoid receptor antagonist (MRA) treatment has led to investigation of new mechanisms that may enhance MR targeted therapies. Recent studies have identified the circadian clock as a novel, reciprocal interacting partner of the MR in the heart. Read More

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Pharmacological Actions of Carbamate Insecticides at Mammalian Melatonin Receptors.

J Pharmacol Exp Ther 2021 02 17;376(2):306-321. Epub 2020 Nov 17.

Department of Pharmacology and Toxicology (G.C.G., A.J.J., R.V.R., M.L.D.), Interdepartmental Neuroscience Program (A.J.J., M.L.D.), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York

Integrated in silico chemical clustering and melatonin receptor molecular modeling combined with in vitro 2-[I]-iodomelatonin competition binding were used to identify carbamate insecticides with affinity for human melatonin receptor 1 (hMT) and human melatonin receptor 2 (hMT). Saturation and kinetic binding studies with 2-[I]-iodomelatonin revealed lead carbamates (carbaryl, fenobucarb, bendiocarb, carbofuran) to be orthosteric ligands with antagonist apparent efficacy at hMT and agonist apparent efficacy at hMT Furthermore, using quantitative receptor autoradiography in coronal brain slices from C3H/HeN mice, carbaryl, fenobucarb, and bendiocarb competed for 2-[I]-iodomelatonin binding in the suprachiasmatic nucleus (SCN), paraventricular nucleus of the thalamus (PVT), and pars tuberalis (PT) with affinities similar to those determined for the hMT receptor. Carbaryl (10 mg/kg i. Read More

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February 2021

Natural products as modulators of retinoic acid receptor-related orphan receptors (RORs).

Nat Prod Rep 2021 04;38(4):757-781

Department of Pharmacognosy, University of Vienna, Vienna, Austria.

Covering: 1994 to 2020 Retinoic acid receptor-related orphan receptors (RORs) belong to a subfamily of the nuclear receptor superfamily and possess prominent roles in circadian rhythm, metabolism, inflammation, and cancer. They have been subject of research for over two decades and represent attractive but challenging drug targets. Natural products were among the first identified ligands of RORs and continue to be of interest to this day. Read More

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The transcriptional repressor REV-ERB as a novel target for disease.

Bioorg Med Chem Lett 2020 09 10;30(17):127395. Epub 2020 Jul 10.

Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, Wood Lane, London W12 0BZ, UK. Electronic address:

REV-ERB is a member of the nuclear receptor superfamily of transcription factors involved in the regulation of many physiological processes, from circadian rhythm, to immune function and metabolism. Accordingly, REV-ERB has been considered as a promising, but difficult drug target for the treatment of numerous diseases. Here, we concisely review current understanding of the function of REV-ERB, modulation by endogenous factors and synthetic ligands, and the involvement of REV-ERB in select human diseases. Read More

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September 2020

Time-Restricted G-Protein Signaling Pathways via GPR176, G, and RGS16 Set the Pace of the Master Circadian Clock in the Suprachiasmatic Nucleus.

Int J Mol Sci 2020 Jul 17;21(14). Epub 2020 Jul 17.

Department of Systems Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyō-ku, Kyoto 606-8501, Japan.

G-protein-coupled receptors (GPCRs) are an important source of drug targets with diverse therapeutic applications. However, there are still more than one hundred orphan GPCRs, whose ligands and functions remain unidentified. The suprachiasmatic nucleus (SCN) is the central circadian clock of the brain, directing daily rhythms in activity-rest behavior and physiology. Read More

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Structure-Based Virtual Screening Accelerates GPCR Drug Discovery.

Trends Pharmacol Sci 2020 06 24;41(6):382-384. Epub 2020 Apr 24.

Université de Paris, Institut Cochin, CNRS, INSERM, F-75014 Paris, France. Electronic address:

Virtual ligand screening (VLS) against high-resolution structures of G-protein-coupled receptors (GPCRs) is likely to become the next-generation drug design approach of choice. Stein and colleagues recently demonstrated the feasibility of such an approach by discovering novel chemical scaffolds for the melatonin MT receptor and compounds with unique in vivo activities. Read More

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Targeting REV-ERBα for therapeutic purposes: promises and challenges.

Theranostics 2020 4;10(9):4168-4182. Epub 2020 Mar 4.

College of Pharmacy, Jinan University, Guangzhou, 510632, China.

REV-ERBα (NR1D1) is a circadian clock component that functions as a transcriptional repressor. Due to its role in direct modulation of metabolic genes, REV-ERBα is regarded as an integrator of cell metabolism with circadian clock. Accordingly, REV-ERBα is first proposed as a drug target for treating sleep disorders and metabolic syndromes (e. Read More

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The IGF/Insulin-IGFBP Axis in Corneal Development, Wound Healing, and Disease.

Front Endocrinol (Lausanne) 2020 3;11:24. Epub 2020 Mar 3.

Department of Ophthalmology, UT Southwestern Medical Center, Dallas, TX, United States.

The insulin-like growth factor (IGF) family plays key roles in growth and development. In the cornea, IGF family members have been implicated in proliferation, differentiation, and migration, critical events that maintain a smooth refracting surface that is essential for vision. The IGF family is composed of multiple ligands, receptors, and ligand binding proteins. Read More

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February 2021

Insilico modeling and analysis of small molecules binding to the PHLPP1 protein by molecular dynamics simulation.

Pak J Pharm Sci 2020 Jan;33(1(Supplementary)):287-294

Department of Bioinformatics and Computational Biology, Virtual University of Pakistan, Lahore, Pakistan.

The PHLPP (Pleckstrin homology domain leucine-rich repeat protein phosphatases) is a newly discovered group of genes which includes PHLPP1 and PHLPP2 and plays an integral part in several cellular processes like apoptosis, cell signaling cell survival, and cell proliferation etc. Both the activation and deactivation of these genes can have vital role in several ailments like heart diseases, circadian rhythm and most importantly the cancer, hence encouraging the growth of novel therapeutic elements. To give new directions into the development of PHLPP1- targeting drugs, the interaction mechanism between PHLPP1 and five important ligands 4IP, B39, 635, ATP and GTA were investigated through docking and Molecular Dynamics Simulation. Read More

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January 2020

Virtual discovery of melatonin receptor ligands to modulate circadian rhythms.

Nature 2020 03 10;579(7800):609-614. Epub 2020 Feb 10.

Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo (SUNY), The State University of New York, Buffalo, NY, USA.

The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT and MT. Circadian release of melatonin at night from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing the physiology and behaviour of animals to the light-dark cycle. The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep and depression. Read More

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Sleep deprivation regulates availability of PrP and Aβ peptides which can impair interaction between PrP and laminin and neuronal plasticity.

J Neurochem 2020 05 5;153(3):377-389. Epub 2020 Feb 5.

Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, Brazil.

PrP is a glycoprotein capable to interact with several molecules and mediates diverse signaling pathways. Among numerous ligands, laminin (LN) is known to promote neurite outgrowth and memory consolidation, while amyloid-beta oligomers (Aβo) trigger synaptic dysfunction. In both pathways, mGluR1 is recruited as co-receptor. Read More

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Characterization of the various functional pathways elicited by synthetic agonists or antagonists at the melatonin MT and MT receptors.

Pharmacol Res Perspect 2020 02 29;8(1):e00539. Epub 2019 Dec 29.

Pôle d'Expertise Biotechnologie Chimie & Biologie Institut de Recherches Servier Croissy-sur-Seine France.

Melatonin is a neurohormone that translates the circadian rhythm to the peripheral organs through a series of binding sites identified as G protein-coupled receptors MT and MT. Due to minute amounts of receptor proteins in target organs, the main tool of studies of the melatoninergic system is recombinant expression of the receptors in cellular hosts. Although a number of studies exist on these receptors, studies of several signaling pathways using a large number of melatoninergic compounds are rather limited. Read More

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February 2020

Cistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet.

Mol Cell 2019 11 6;76(4):531-545.e5. Epub 2019 Nov 6.

Institute for Diabetes and Obesity (IDO), Helmholtz Center Munich (HMGU) and German Center for Diabetes Research (DZD), Ingolstaedter Landstr. 1, 85764 Neuherberg (Munich), Germany; Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich (HMGU) and German Center for Diabetes Research (DZD), Ingolstaedter Landstr. 1, 85764 Neuherberg (Munich), Germany; Metabolic Programming, School of Life Sciences Weihenstephan, Gregor Mendel Str. 2, 85354 Freising, Technische Universitaet Muenchen (TUM), Munich, Germany. Electronic address:

The glucocorticoid receptor (GR) is a potent metabolic regulator and a major drug target. While GR is known to play integral roles in circadian biology, its rhythmic genomic actions have never been characterized. Here we mapped GR's chromatin occupancy in mouse livers throughout the day and night cycle. Read More

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November 2019

Heme binding to human CLOCK affects interactions with the E-box.

Proc Natl Acad Sci U S A 2019 10 16;116(40):19911-19916. Epub 2019 Sep 16.

School of Chemistry, University of Bristol, BS8 1TS Bristol, United Kingdom;

The circadian clock is an endogenous time-keeping system that is ubiquitous in animals and plants as well as some bacteria. In mammals, the clock regulates the sleep-wake cycle via 2 basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain proteins-CLOCK and BMAL1. There is emerging evidence to suggest that heme affects circadian control, through binding of heme to various circadian proteins, but the mechanisms of regulation are largely unknown. Read More

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October 2019

Basophil degranulation in response to IgE ligation is controlled by a distinctive circadian clock in asthma.

Allergy 2020 01 23;75(1):158-168. Epub 2019 Oct 23.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, Italy.

Background: Several factors may contribute to the circadian variability of clinical manifestations in asthma and allergy. Basophils play a pivotal role in allergic inflammation. However, evidence for a functional clock governing the effector function of these cells is sparse and contradictory. Read More

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January 2020

Metabolic and behavioral parameters of mice with reduced expression of Syndecan-1.

PLoS One 2019 12;14(7):e0219604. Epub 2019 Jul 12.

Düsseldorf University Hospital, Department of OB/GYN and REI (UniKiD), Düsseldorf, Germany.

Energy balance is essential for all species. Ligand-receptor interactions mediate processes that regulate body activities like reproduction and metabolism based on the energy status. Such receptors are the heparan sulfate proteoglycans and specifically the family of syndecans. Read More

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Update on Restless Legs Syndrome: from Mechanisms to Treatment.

Curr Neurol Neurosci Rep 2019 06 27;19(8):54. Epub 2019 Jun 27.

Department of Neurology, Feinberg School of Medicine, Chicago, IL, USA.

Purpose Of Review: To provide an overview of the molecular pathways and recent genetic risk loci associated with restless legs syndrome/Willis-Ekbom disease (RLS/WED) and describe the most recent treatment guidelines.

Recent Findings: Diagnostic criteria for RLS/WED now include a fifth criterion to differentiate from RLS/WED mimics. Our understanding of disease pathophysiology has improved, specifically regarding iron regulation in the brain and the role of other pathways such as opioid signaling and brain and spinal cord circuitry may play. Read More

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SR9009 has REV-ERB-independent effects on cell proliferation and metabolism.

Proc Natl Acad Sci U S A 2019 06 24;116(25):12147-12152. Epub 2019 May 24.

Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104;

The nuclear receptors REV-ERBα and -β link circadian rhythms and metabolism. Like other nuclear receptors, REV-ERB activity can be regulated by ligands, including naturally occurring heme. A putative ligand, SR9009, has been reported to elicit a range of beneficial effects in healthy as well as diseased animal models and cell systems. Read More

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