ArticleScience signaling2013
Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed, 145 citations in OpenAlex.
- Article
- Selective GPR17 antagonism enhances structural and functional recovery in animal models of demyelination.PloS one · 2026Article
- Review
- Discovery of novel and selective GPR17 antagonists as pharmacological tools for developing new therapeutic strategies in diabetes and obesity.European journal of medicinal chemistry · 2025Article
- G Protein-Coupled Receptor 17 Inhibits Glucagon-like Peptide-1 Secretion via a Gi/o-Dependent Mechanism in Enteroendocrine Cells.Biomolecules · 2024Article
- Leukotriene signaling in neurodegeneration: implications for treatment strategies.Inflammopharmacology · 2024Review
- G protein-coupled receptor 17 inhibits glucagon-like peptide-1 secretion via a Gi/o-dependent mechanism in enteroendocrine cells.bioRxiv : the preprint server for biology · 2024Article
- Nrg1 intracellular signaling regulates the development of interhemispheric callosal axons in mice.Life science alliance · 2024Article
- The leukotriene receptor antagonist montelukast as a potential therapeutic adjuvant in multiple sclerosis - a review.Frontiers in pharmacology · 2024Review
- G Protein Coupled Receptors Potentially Involved in Oligodendrogenesis: A Gene Expression Analysis.Iranian journal of public health · 2022Article
- Leukotrienes vs. Montelukast-Activity, Metabolism, and Toxicity Hints for Repurposing.Pharmaceuticals (Basel, Switzerland) · 2022Review
- A Glance at the Molecules That Regulate Oligodendrocyte Myelination.Current issues in molecular biology · 2022Review
- A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action.Journal of cell communication and signaling · 2022Review
- Intestinal Gpr17 deficiency improves glucose metabolism by promoting GLP-1 secretion.Cell reports · 2022Article
- The oligodendrocyte-enriched orphan G protein-coupled receptor Gpr62 is dispensable for central nervous system myelination.Neural development · 2021Article
- Involvement of GPR17 in Neuronal Fibre Outgrowth.International journal of molecular sciences · 2021Article
- Synthesis and Preclinical Validation of Novel Indole Derivatives as a GPR17 Agonist for Glioblastoma Treatment.Journal of medicinal chemistry · 2021Article
- Targeting Orphan G Protein-Coupled Receptor 17 with T0 Ligand Impairs Glioblastoma Growth.Cancers · 2021Article
- Conserved residues in the extracellular loop 2 regulate Stachel-mediated activation of ADGRG2.Scientific reports · 2021Article
- G-protein-coupled receptor GPR17 inhibits glioma development by increasing polycomb repressive complex 1-mediated ROS production.Cell death & disease · 2021Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 1 institution in 1 country.
Funding
Abstract
Replacement of the lost myelin sheath is a therapeutic goal for treating demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS). The G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) GPR17, which is phylogenetically closely related to receptors of the "purinergic cluster," has emerged as a modulator of CNS myelination. However, whether GPR17-mediated signaling positively or negatively regulates this critical process is unresolved. We identified a small-molecule agonist, MDL29,951, that selectively activated GPR17 even in a complex environment of endogenous purinergic receptors in primary oligodendrocytes. MDL29,951-stimulated GPR17 engaged the entire set of intracellular adaptor proteins for GPCRs: G proteins of the Gα(i), Gα(s), and Gα(q) subfamily, as well as β-arrestins. This was visualized as alterations in the concentrations of cyclic adenosine monophosphate and inositol phosphate, increased Ca²⁺ flux, phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), as well as multifeatured cell activation recorded with label-free dynamic mass redistribution and impedance biosensors. MDL29,951 inhibited the maturation of primary oligodendrocytes from heterozygous but not GPR17 knockout mice in culture, as well as in cerebellar slices from 4-day-old wild-type mice. Because GPCRs are attractive targets for therapeutic intervention, inhibiting GPR17 emerges as therapeutic strategy to relieve the oligodendrocyte maturation block and promote myelin repair in MS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.