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Alex Serafini  pointed out in his interview, Regulators of G protein Signaling (RGS proteins)  might GPCRs as tangential but inevitable: "I feel like I never was particularly explicitly interested in GPCR signaling Whether working on opioid withdrawal, addiction vulnerability, or chronic pain, GPCR-related signaling repeatedly emerged as the core mediator  — demonstrating the reach of these signaling pathways beyond signaling .

Questions about how opioids impair breathing, why xylazine complicates interventions, and how receptor-level While writing a literature review on opioid and alcohol addiction susceptibility, something shifted. “That was kind of a signal to me that maybe I should start thinking about a PhD,” Catherine recalls. She is especially interested in mu-opioid receptor signaling  and how xylazine, as an alpha-2 adrenergic Instead, she followed the signals that kept her engaged and energized.

October 2022 Coincident Regulation of PLCβ Signaling by Gq-Coupled and μOpioid Receptors Opposes Opioid The primary analgesic target of opioids is the μ-opioid receptor (MOR). Here we investigated a potential mechanism for regulation of PLC signaling downstream of MOR in HEK293 cells and found that MOR alone could not stimulate PLC, but rather required a coincident signal from These data support a model where Gq and Gβγ-dependent signaling cooperatively regulate PLC activation

Redefining Opioid Pharmacology Ben and his colleagues discovered that PAMs can dramatically increase the efficacy of existing opioids. “We’ve seen these modulators rescue opioid function where it completely fails in neuroma models. Beyond Acute Pain: Into the Chronic Unknown Opioids work well for acute pain. Chronic pain? Neuropathic conditions like neuromas often resist standard opioid treatments.

August 2022 "Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled

paper highlights: GLP-1R/GIPR biased agonism enhances metabolic outcomes Ghrelin receptor flips D2 signaling emphasizes scaffold selection, linker optimization, and assay compatibility to enhance target binding and signal Constitutive ghrelin receptor activity, not dimerization or ligand binding —reverses dopamine D2 signaling A MOR-positive allosteric modulator (BMS-986122) selectively enhances opioid signaling  through specific

Opioid receptors are G-protein-coupled receptors (GPCRs) part of cell signaling paths of direct interest The potentially low pH at tissue targeted by opioid drugs in pain management could impact drug binding to the opioid receptor, because opioid drugs typically have a protonated amino group that contributes In this review, we discuss the relationship between structure, function, and dynamics of opioid receptors from the perspective of the usefulness of computational studies to evaluate protonation-coupled opioid-receptor

: GPCR Science Meets Public Health At its core, Catherine Demery’s research  is about receptors and signaling pathways—how mu-opioid  and alpha-2 adrenergic receptors  interact to disrupt breathing. And because naloxone only targets opioids, it cannot reverse xylazine. By displacing opioids from the mu-opioid receptor, it restores breathing within minutes. For Catherine, those numbers aren’t just statistics—they’re signals guiding how to build better models

September 2022 Fentanyl activates ovarian cancer and alleviates chemotherapy-induced toxicity via opioid receptor-dependent activation of EGFR "Background Fentanyl is an opioid analgesic and is widely used Immunoblotting approach was used to analyze signaling involved in fentanyl’s action focusing on EGFR.

There, she chose to write a review on genetic variation in susceptibility to alcoholism and opioid addiction—a Returning to the Opioid Questions That Mattered Now, as a PhD candidate in the Traynor and Anand labs at the University of Michigan, Catherine is focused on the mechanisms of opioid-induced respiratory "I've always been really passionate and somewhat sensitive to people who struggle with opioid abuse.

September 2022 To probe the activation mechanism of the Delta opioid receptor by an agonist ADL5859 started from inactive conformation using molecular dynamic simulations "The δ-opioid receptor (DOR) is a critical

September 2022 "Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid only slight structural changes compared to morphine, exhibits inhibitory effect, and is used to treat opioid

The company’s scientific approach relied on targeting GPCRs — specifically opioid receptors — using biased to bring a novel, safer class of pain therapeutics to patients — an urgent need in the midst of the opioid Superluminal Medicines: AI/ML Meets GPCR Pharmacology As Ajay continued to explore how GPCR signaling The company’s goal is to model receptor dynamics — including biased signaling — to predict drug behavior

Breakthroughs this week: Decoding ADGRE5 signaling; Eli Lilly’s obesity pill vs Novo’s Wegovy; Certa and Novo Upcoming events:  September GPCR symposia across Europe, UK, and online—including neuroGPCR signaling Must-read publications:  Tryptophan-cholic acid and MRGPRE in glucose homeostasis; Biased signaling in With Premium, you move faster, smarter, and more confidently than peers relying on scattered signals. Those who act on the right signals today will lead tomorrow’s breakthroughs—and avoid delays others won

Biased signalling and allosteric machines: new vistas and challenges for drug discovery. Allosteric modulation of G protein-coupled receptor signaling. Science signaling. 2024;17(841):eadi4747. 37.         Science signaling. 2024;17(843):eabq7038. 38.         Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief

It’s about chasing a signal through the noise. She went from reluctant intern to global researcher shaping how we understand GPCR spatial signaling. Luck, Leadership & GPCR Signaling Michelle is clear: luck played a role. But so did choice. of Signaling laboratory, asking a deceptively simple question: where  do GPCR signals happen—and how Spatial signaling isn’t just a technical detail. It’s a new language for drug discovery.

Regulator G protein Signaling (RGS) proteins are critical components of the intracellular signaling pathways and amplitude of GPCR signaling. For example, μ opioid receptor (MOR) interacts with Gαi/o and Gαz subunits, which have a slow enzymatic Senese, N.B., et al., Regulator of G-Protein Signaling (RGS) Protein Modulation of Opioid Receptor Signaling Traynor, Differential modulation of mu- and delta-opioid receptor agonists by endogenous RGS4 protein

bridge foundational receptor theory with today’s most pressing pharmacological questions, from biased signaling Read Maria’s Story GPCR Publication Highlights   CXCR4 signaling promotes terminal erythropoiesis  through

Opioid receptors belong to class A of G protein-coupled receptors or GPCRs and signaled mainly through Therefore, the study of the different signal transductions triggered by the opioid-receptor interaction downstream through different signaling pathways triggered by different molecules2. Therefore to understand better the functions of arrestins in MOR signaling, Shiraki et al., explored the function of β-arrestin 2 in MOR signaling using the SH-SY5Y cell line that endogenously expresses

applications of Nbs to facilitate the development of more selective drugs capable of modulating specific signaling Nb39: This nanobody was identified for the μ-opioid receptor (μOR) and also increased the affinity of

When it comes to signal transduction, cellular context matters. to scaffold various kinases and modulate downstream signaling pathways. can be activated by ligands and initiate signaling cascades. , sustained signaling responses from intracellular compartments can be regulated by the kinetics of signaling Compartmentalized GPCR Signaling from Intracellular Membranes.

bound to these interaction partners available today do not reveal a clear conformational basis for signaling

vast family of membrane-bound proteins crucial for transmitting external stimuli into intracellular signals Gi/o, Gq/11, and G12/13, at the initial GPCR-G protein association step, ensuring precise downstream signalling Instead, G12 overexpression inhibited V2R downstream signalling, including β-arrestin recruitment and This unproductive coupling revealed that non-cognate G protein interactions could modulate GPCR signalling Gupte, T.M., et al., Priming GPCR signaling through the synergistic effect of two G proteins. 

One fascinating aspect of the cellular signaling network is the crosstalk between G protein-coupled receptors while promoting constitutive Gβγ signaling. localization and signaling efficiency. intervention in diseases characterized by dysregulated signaling pathways. Science signaling, 17(839), eade8041. https://doi.org/10.1126/scisignal.ade8041

G protein-coupled receptors (GPCRs) activation assumes that stimulation of heterotrimeric G protein signaling In this model, GPCR signaling is turned-off by receptor phosphorylation via GPCR kinases (GRKs) and subsequent the last decade, this model has been extended by discovering that some internalized GPCRs continue to signal Accumulative evidence shows that the location of signaling has an impact on the physiological effects of GPCR signaling.

We will discuss recent evidence as well as what we consider as emerging areas to explore; from the signalling relevance of these interactions, since this additional level of molecular cross-talk between receptors and signaling

regulation of mTORC1 by upstream stimuli, with a specific focus on G-protein coupled receptor (GPCR) signaling

October 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence presents treatment challenges. Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease. The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in the pathogenesis of dementia. Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst improving cognition and memory. In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic potential of A1 and A2A receptors. 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 may increase drug discovery success and enhance the therapeutic response." Read more at the source #DrGPCR #GPCR #IndustryNews

protein-coupled receptors (GPCRs) are membrane-bound proteins that sense external stimuli and relay signals For example, dimerization has been shown to affect signaling pathways in class A dopamine receptors like homodimers and heterodimers, which may play a crucial role in modulating receptor function and ligand signaling decreased high-affinity binding to its natural ligand, GLP-1, while selectively affecting receptor signaling Perreault, M.L., et al., Heteromeric dopamine receptor signaling complexes: emerging neurobiology and

August 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence presents treatment challenges. Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease. The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in the pathogenesis of dementia. Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst improving cognition and memory. In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic potential of A1 and A2A receptors. 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 may increase drug discovery success and enhance the therapeutic response." Read more at the source #DrGPCR #GPCR #IndustryNews