Search Results
521 items found for "Jespers W"
- The regulation of PKA signaling in obesity and in the maintenance of metabolic health
While limited, human studies infer differential regulation of the PKA system in obese compared to lean
- Protein Uncoupling as an Innovative Practice in Diabetes Mellitus Treatment: A Metabolic Disorder
then reduce mitochondrial free radical production, potentially protecting diabetes mellitus patients who Objectives: The objectives of the study are to find out the newest ways to treat diabetes mellitus through
- G protein-biased GPR3 signaling ameliorates amyloid pathology in a preclinical Alzheimer's disease..
October 2022 "Biased G protein-coupled receptor (GPCR) ligands, which preferentially activate G protein Our previous work demonstrated that GPR3-mediated β-arrestin signaling modulates amyloid-β (Aβ) generation adverse phenotypes, including elevated anxiety-like behavior, reduced fertility, and memory impairment, which We further determined that G protein-biased signaling reduces soluble Aβ levels and leads to a decrease The changes in amyloid pathology are accompanied by robust microglial and astrocytic hypertrophy, which
- The microglial endocannabinoid system similarly regulated by lipopolysaccharide and interferon gamma
Past work has produced conflicting results with respect to the effects of pro-inflammatory conditions Thus, we systematically investigated the relationship between the concentration of two distinct pro-inflammatory lipopolysaccharide and interferon gamma, on the abundance of components of the endocannabinoid system within Here we show that lipopolysaccharide and interferon gamma influence messenger RNA abundances of the microglial Furthermore, we demonstrate that the efficacy of different synthetic cannabinoid treatments with respect
- Label-free LC-MS based assay to characterize small molecule compound binding to cells
Here we developed and validated a label-free, liquid chromatography-mass spectrometry (LC-MS) based cell This assay was applied to various target classes, with particular emphasis on those for which protein-based In one example, to study a G protein coupled receptor (GPCR), we used one antagonist as probe and multiple In another example, this assay was applied to an ion channel target with its agonists, of which the determined
- Developing the Cannabinoid Receptor 2 (CB2) pharmacopoeia: past, present, and future
A diverse pharmacopoeia of cannabinoid ligands is available, which has led to considerable advancements However, until recently, most CB2 ligands were highly lipophilic and as such not optimal for clinical We review the current state of CB2 ligand development and progress in optimising physicochemical properties
- Pepducin-mediated G Protein-Coupled Receptor Signaling in the Cardiovascular System
We will discuss the historic context of pepducin development for each receptor, as well as the structural
- Bell-Evans model and steered molecular dynamics in uncovering the dissociation kinetics of ligands..
Screening drug candidates in terms of their computationally predicted residence times, which is a measure Here, we have implemented an optimized approach of combining the data derived from steered molecular We have predicted the absolute ligand residence times on the timescale of seconds. However, our predictions were many folds shorter than those determined experimentally. studies were identified.
- Dr. GPCR Virtual Cafe with Matthew Eddy - New date!
☕ We are excited to announce our rescheduled Dr. GPCR Virtual Cafe session with Dr. It's a great opportunity to get warmed up for the upcoming Summit starting the next Monday.
- Dr. GPCR Virtual Cafe - Postponed
We are postponing the Dr. We will provide a new rescheduling date soon. #gpcr #drgpcr
- Developing the Cannabinoid Receptor 2 (CB2) pharmacopeia: past, present, and future
A diverse pharmacopeia of cannabinoid ligands is available, which has led to considerable advancements However, until recently, most CB2 ligands were highly lipophilic and as such, not optimal for clinical We review the current state of CB2 ligand development and progress in optimizing physicochemical properties
- TRPM3 in the eye and in the nervous system - from new findings to novel mechanisms
However, the channel is expressed in various tissues and cell types including neurons as well as glial In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene.
- Community guidelines for GPCR ligand bias: IUPHAR review 32
Depending on which ligand activates a receptor, it can engage different intracellular transducers. This 'biased signalling' paradigm requires that we now characterize physiological signalling not just Here, we provide guidelines and terminology for any scientists to design and report ligand bias experiments
- Molecular insights into psychedelic drug action
Here we review the current knowledge regarding the molecular details of psychedelic drug actions and
- Molecular targets of psychedelic-induced plasticity
Here we discuss some of the most recent findings in human studies and contextualize them considering
- AlphaFold2 versus experimental structures: evaluation on G protein-coupled receptors
August 2022 "As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide Herein we evaluated the accuracy of GPCR structure models predicted by AlphaFold2. We revealed that AlphaFold2 could capture the overall backbone features of the receptors. However, the predicted models and experimental structures were different in many aspects including the use of predicted structure models in the functional study and structure-based drug design of GPCRs, which
- Adenosine receptor signalling in Alzheimer's disease
Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic Although there are no available medicines targeting these receptors approved for treating dementia, we provide insights into some novel strategies, including allosterism and the targeting of oligomers, which
- GRK2 in cardiovascular disease and its potential as a therapeutic target
G protein-coupled receptors (GPCRs) are critical myocardial signal transducers which regulate cardiac Additionally, the GRK2 interactome includes numerous proteins which interact with differential domains
- Posttranslational modifications in GPCR internalization
internalization dynamics, internalization routes, postinternalization fates, and related diseases, which
- Diversity and specificity in location-based signaling outputs of neuronal GPCRs
August 2022 "The common mechanisms by which members of the G protein-coupled receptor (GPCR) family respond to neurotransmitters in the brain have been well studied. Here we will discuss recent studies on the diversity of location, effectors, and signaling of GPCRs,
- Deciphering the signaling mechanisms of β-arrestin1 and β-arrestin2 in regulation of cancer cell...
cycle and metastasis "β-Arrestins are ubiquitously expressed intracellular proteins with many functions which interact directly and indirectly with a wide number of cellular partners and mediate downstream signaling Originally, β-arrestins were identified for their contribution to GPCR desensitization to agonist-mediated delivers a concise overview of the role of β-arrestins with a primary emphasis on the signaling processes which
- Structural basis of GPCR coupling to distinct signal transducers: implications for biased signaling
interaction partners available today do not reveal a clear conformational basis for signaling bias, which would have enabled the rational design of biased GRCR ligands.
- Synthesis and characterization of an orally bioavailable small molecule agonist of the apelin recept
Previously, we had identified a novel pyrazole-based agonist 1 ((S)-N-(1-(cyclobutylamino)-1-oxo-5-(piperidin
- Fluorescent Ligands Targeting Intracellular Allosteric Binding Site of the Chemokine Receptor CCR2
Here, we report the structure-based development of fluorescent ligands targeting the intracellular allosteric reported intracellular CCR2 antagonists, several tetramethylrhodamine (TAMRA)-labeled CCR2 ligands were By means of these studies, we developed 14 as a fluorescent CCR2 ligand, enabling cell-free as well Further, we show that 14 can be used as a tool for fragment-based screening approaches.
- Exploring pharmacological inhibition of G q/11 as an analgesic strategy
Experimental approach: We used a series of behavioural assays to evaluate the acute responses of mice to painful thermal stimulation while administering YM-254890 alone and in combination with morphine. We then used electrophysiological recordings to evaluate the effects of YM-254890 on the excitability
- A NanoBRET-Based H 3 R Conformational Biosensor to Study Real-Time H 3 Receptor Pharmacology in...
We recently reported the initial characterization of a NanoBRET-based conformational histamine H3 receptor In the current study, we have further characterized this H3R biosensor on intact cells by monitoring In addition, we have validated the H3R biosensor in membrane preparations and found that observed potency values better correlated with binding affinity values that were measured in radioligand competition
- Luciferase-based GloSensor™ cAMP assay: Temperature optimization and application to cell-based kinet
Monitoring intracellular cAMP levels can help identify orthosteric agonists and antagonists, as well As well, it has not been reported whether the effects of temperature on biosensor activity are reversible Here, we describe the temperature sensitivity and reversibility of the GloSensor™ cAMP assay, and which We also present a detailed protocol for monitoring cAMP levels in live cells expressing endogenous or We found that preincubation and luminescence reading at room temperature were optimal as compared to
- In vivo detection of GPCR-dependent signaling using fiber photometry and FRET-based biosensors
Many such biosensors are based on the principle of Förster resonance energy transfer (FRET), and we have By combining fiber photometry with FRET-based biosensors, we were able to track GPCR-dependent signaling Recording from specific neuronal populations, we can quantify intracellular signaling while simultaneously This methodology would be compatible with other mammalian species and with many biosensors. Hence, it has wide applicability across a spectrum of neuroscience research, ranging from the study of