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Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment of Non-Alcoholic Fatty Liver Disease The prevalence of non-alcoholic fatty liver disease (NAFLD) is Gaining control over disease-related events in non-alcoholic steatohepatitis (NASH), an advanced form

lipopolysaccharide (LPS) and TNFα suggests that it may play a role in the development of inflammatory and fibrotic diseases.

October 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic

August 2022 "Alzheimer's disease (AD) is the most common dementia in the elderly and its increasing prevalence Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer's disease In this review, we provide an accessible summary of the literature on Alzheimer's disease and the therapeutic

August 2022 "Cardiovascular diseases (CVDs) represent the leading cause of death globally.

chemotaxis of leukocytes, especially neutrophils, during inflammation, a key process in cardiovascular disease

chemotaxis of leukocytes, especially neutrophils, during inflammation, a key process in cardiovascular disease

April 2022 "By Sophie Bradley | Apr 12, 2022 Summary Sophie Bradley, Translational Sciences Associate Director at Sosei Heptares, recently presented at the Keystone Symposia GPCR Conference, a summary of work performed both at Sosei Heptares and Glasgow University characterizing the role of the muscarinic M1 receptor in cognitive and neurodegenerative disorders and the potential therapeutic benefit of muscarinic M1 selective ligands." Read more at the source #DrGPCR #GPCR #IndustryNews

normal glutamate transmission has been implicated in a variety of neurodegenerative and neuropsychiatric diseases contribution of mGluR2 and mGluR3 to the pathophysiology of some neurodegenerative and neuropsychiatric diseases including Amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's diseases

October 2022 Novel Therapies for Cardiometabolic Disease: Recent Findings in Studies with Hormone Peptide-Derived diabetes (T2DM) is provoking an important socioeconomic burden mainly in the form of cardiovascular disease

September 2022 "Parkinson’s disease (PD) as a progressive neurodegenerative disorder arises from multiple

pathways, are leading to the development of drugs with superior efficacy and reduced side effects in heart disease Although GPCRs are implicated in the pathophysiology of Alzheimer's disease (AD), biased GPCR signaling

August 2022 "Several G-protein coupled receptors (GPCR) are upregulated in Alzheimer's Disease (AD),

Hodson: physiology, disease context, and imaging logic JB: chemistry, ligand engineering, mechanistic

Following the Data Into GPCR, Metabolic Disease and GLP-1 After his PhD, Hodson entered neuroendocrinology Hodson wanted to contribute to a disease that affects millions. unique model: Rich in GPCR signaling pathways Experimentally accessible Deeply relevant to metabolic disease The Future of GPCR Therapeutics in Metabolic Disease Even with GLP-1 and GIP agonists reshaping diabetes

Watch Episode #177 Some scientific breakthroughs don’t start with a grant or a perfectly architected project plan. They start with a chance email, an unexpected visitor at the door, or the moment a team realizes the question in front of them is simply too big for one mind. In research, including the GPCR world collaboration isn’t a luxury. It’s survival. The future of discovery will belong to scientists who know how to build the right partnerships and stay humble enough to let others’ strengths unlock their own. The GPCR Collaboration Mindset Behind Breakthrough Science Most researchers have a story about the moment they realized they couldn’t push their science any further alone. For Hodson, that moment came early. His career moved through veterinary school, immunology, neuroendocrinology, and finally into islet biology — each step revealing a simple truth: Complex problems require multiple minds. By the time his lab began dissecting the GLP-1 and GIP receptor landscape in islets and brain, the signal became undeniable. GPCR signaling wasn’t linear. It wasn’t clean. And it certainly wasn’t something a single lab could unpick with isolated tools. To understand how incretin receptors behave in intact tissue, Hodson needed people who saw problems differently — chemists, structural biologists, cryo-EM experts, genetics teams, and collaborators who could challenge his assumptions without ego. That mindset shaped his partnership with JB, the chemist who would eventually help his lab visualize receptors in living systems with far more precision than antibodies ever allowed. Their collaboration didn’t start as a big strategic play. It started with curiosity, openness, and the humility to admit that better answers required better tools — and those tools lived in someone else’s expertise. How GPCR Collaboration Bridges Chemistry and Physiology Great collaborations often begin where frustrations peak. For years, the GPCR community wrestled with unreliable antibodies. Some worked in one tissue but failed in another. Some detected off-targets. And some simply misled entire research programs. Hodson’s group felt the impact directly: imaging incretin receptors in intact islets and brain slices was nearly impossible. That changed when JB’s team walked in with a different lens. Chemists don’t look at receptors the way physiologists do. They think in functional groups, fluorophores, linkers, and binding pockets. And that perspective unlocked something powerful. Instead of forcing antibodies to do what they weren’t built for, JB’s group engineered fluorescent ligands based on known GLP-1 and GIP pharmacology. The result was a set of chemical probes that finally allowed researchers to visualize where receptors exist, how drugs access them, and what cell types respond. These tools didn’t appear because someone wrote “visualize GPCRs better” in a grant. They appeared because one lab’s bottleneck became another lab’s engineering challenge — and together, they solved something neither could crack alone. This collaboration reshaped the way Hodson’s lab studies receptor biology. It didn’t replace physiology with chemistry. It fused them, creating a hybrid view of receptor signaling that has now been adopted by labs worldwide. When GPCR Collaboration Makes the Data Finally Click Every long collaboration earns a breakthrough moment — often after months or years of confusion. For Hodson, that moment came with a protein he’d been tracking for a decade: vitamin D binding protein, a glucagon-related secretion from alpha cells. For years, the data made no sense. The signaling didn’t line up. The knockout behaved differently than expected. And interactions with GLP-1 pathways were inconsistent. Most scientists would have shelved the project. Hodson nearly did. The turning point came when the cryo-EM data arrived — a structure solved through the same collaborative network that had built the fluorescent tools. Suddenly, the anomalies aligned. The protein was interacting with GPCRs in a way that no single technique could reveal. Chemistry, imaging, physiology, and structure finally intersected. This is the power of collaboration in GPCR research: insights emerge when one group’s “weird data” becomes another group’s missing puzzle piece. And when those pieces come together, the field jumps forward faster than any lab could push it alone. Why GPCR Collaboration Is Essential for Modern Science Hodson makes the point bluntly: modern GPCR science requires specialists. You need genetics teams for variant interpretation, metabolic phenotyping facilities for in vivo work, structural experts for cryo-EM, chemists for tool development, and data scientists who can integrate everything. No one person can be excellent at all of it — and pretending otherwise slows discovery. The shift toward team science isn’t cultural. It’s technical. The questions are larger, the stakes higher, and the datasets more complex. Collaboration is not “nice to have.” It is the only path to meaningful discovery. And it’s not just about capability. It’s about trust — the kind of trust built when collaborators confirm your data, replicate your results, and call out your blind spots before reviewers do. Hodson and JB’s collaboration works not because their skills align but because their thinking styles differ. One pushes chemistry further. The other pushes physiology deeper. Together, they push GPCR science faster. The Future of GPCR Collaboration in Metabolic Research The next decade of metabolic research won’t hinge on a single target. It will hinge on the teams who can map GPCR signaling with precision and design therapies that fit real biology — not idealized models. From GLP-1 and GIP dual agonists to the growing field of GPCR-based delivery systems, collaboration will control the pace of innovation. Here’s where the biggest opportunities will emerge: Building receptor-specific delivery systems for gene or peptide therapeutics Mapping cell-type–specific GPCR signaling in metabolic tissues Using genetics to understand responder vs. non-responder profiles Developing muscle-sparing metabolic therapies by combining GPCR pathways Creating chemical tools that finally show how drugs reach their targets These aren’t solo-lab problems. They’re team problems — the kind that require chemistry, physiology, pharmacology, structural biology, computational modeling, and clinical insight working as one system. The labs that collaborate boldly will discover faster, validate better, and translate more effectively. This is where GPCR science is heading: toward deeper integration, shared tools, and partnerships that amplify what each discipline does best. This conversation is part of a three episode series produced in collaboration with our partners at Celtarys Research . If this story resonates with your work or curiosity, go deeper. 🎧 Listen to the full conversation with Dr. David Hodson

focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases

Positive Phase 3 Data for KINECT-HD Study Evaluating Valbenazine for Chorea Associated with Huntington Disease Statistically Significant Reduction in Chorea Movements (p < 0.0001) as Measured by the Unified Huntington's Disease inhibitor being investigated as a once-daily treatment in adults with chorea associated with Huntington disease met the primary endpoint of reduction in severity of chorea, the cardinal motor feature in Huntington disease , as measured by change in the Unified Huntington's Disease Rating Scale (UHDRS®) Total Maximal Chorea

Acquired hypocalciuric hypercalcemia (AHH) is a rare disease caused by calcium-sensing receptor (CaSR follows: (a) elderly (74-87 years at diagnosis), (b) male, (c) unexpectedly showed no other autoimmune diseases

Confo Therapeutics receives €1.7 million VLAIO grant for further research on GPCR modulators for rare diseases

September 2022 β2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic during Collagen-Induced Arthritis "The sympathetic nervous system (SNS) has either a pro-inflammatory or anti-inflammatory effect, depending on the stage of arthritis. In the past, treatment of arthritic B cells with a β2-adrenergic receptor (β2-ADR) agonist has been shown to attenuate arthritis. In this study, the expression and signaling of β2-ADR in B cells during collagen-induced arthritis (CIA) were investigated to provide an explanation of why only B cells from arthritic mice are able to improve CIA. Splenic B cells were isolated via magnetic-activated cell sorting (MACS). Adrenergic receptors on B cells and intracellular β2-ADR downstream molecules (G protein-coupled receptor kinase 2 (GRK-2), β-Arrestin 2, p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB)) were analyzed at different time points in naïve and arthritic B cells with and without stimulation of β2-ADR agonist terbutaline by flow cytometry. β2-ADR-expressing B cells increase during CIA without a change in receptor density. Moreover, we observed a profound downregulation of GRK-2 shortly after induction of arthritis and an increase in β-Arrestin 2 only at late stage of arthritis. The second messengers studied (p38, ERK1/2 and CREB) followed a biphasic course, characterized by a reduction at onset and an increase in established arthritis. Stimulation of CIA B cells with the β-ADR agonist terbutaline increased pp38 MAPK independent of the timepoint, while pERK1/2 and pCREB were enhanced only in the late phase of arthritis. The phosphorylation of p38 MAPK, ERK1/2 and CREB in the late phase of arthritis was associated with increased IL-10 produced by B10 cells. The change of β2-ADR expression and signaling during sustained inflammation might be an integral part of the switch from pro- to anti-inflammatory action of sympathetic mechanisms in late arthritis." Read more at the source #DrGPCR #GPCR #IndustryNews

We also review the hierarchy of signaling events driving the fibrotic response and the communications

as sensory perception, reproduction, development, growth, metabolism, and are also linked to major diseases , such as neuroinflammatory, metabolic and autoimmune diseases. immune cells in a range of pro‐inflammatory disorders renders it a promising target in inflammatory and fibrotic GPR84 has been additionally proposed to be a potential biomarker in different inflammatory diseases ( GPR84 is a promising target to exploit and the investment in better tools to study its function in both disease

We showed that cGAS expression was induced in fibrotic liver and kidney, but suppressed in endothelial

of the Clinical Candidate IDOR-1117-2520: A Potent and Selective Antagonist of CCR6 for Autoimmune Diseases with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic

for developing successful therapeutics , particularly for neurological disorder and neurodegenerative diseases This includes diseases such as depression, Parkinson’s, schizophrenia, and Alzheimer’s. GPCRs play a central role in neuronal signaling and have been used to treat these diseases with varying Thus, they also participate in numerous diseases. disease.

Tom Sakmar points to a largely overlooked mechanism  in disease: autoantibodies that don’t block receptors A New Role for GPCRs in Disease Sakmar highlights how endothelial cells, which express a wide array of pathological signaling.” — Tom Sakmar This makes them more than biomarkers — they’re potential drivers of disease

Alexander Hauser, Caroline Gorvin et al. for their research on GPCR gene variants and human genetic disease of glycosaminoglycans in GPCR signaling G protein-coupled receptor-mediated autophagy in health and disease organelles Reviews, GPCRs, and more G protein-coupled receptor (GPCR) gene variants and human genetic disease Heptares Doses First Subject in Phase 1 Trial with HTL0033744, an EP4 Agonist for Inflammatory Bowel Disease Ownership from GSK of HTL0027477, a Clinic-ready, First-in-Class Oral GPR35 Agonist for Inflammatory Bowel Disease

high maternal mortality, is a risk factor highly associated with maternal and offspring cardiovascular disease Obesity, immunological diseases and endocrine metabolic diseases are high-risk factors for the development them, the secretin/adhesion (Class B) G protein-coupled receptors are essential drug targets for human diseases , such as endocrine diseases and cardiometabolic diseases.

monoclonal antibodies for the treatment of cancer, infections, metabolic disorders or inflammatory diseases Recently, functional autoantibodies targeting GPCRs have been associated with various disease-specific is to bring together the current knowledge on the role of autoantibodies targeting GPCRs in various diseases , such as cardiovascular diseases, renal diseases, autoimmune diseases such as systemic sclerosis or