ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2016
The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.Science advances · 2026Article
- Targeting GPCR Signaling in Parkinson's Disease: From Molecular Pathology to Exercise-Based Therapeutics.Molecular neurobiology · 2026Review
- The Role and Mechanisms of G protein-coupled receptors in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia.Translational psychiatry · 2025Review
- Receptors on Microglia.Advances in neurobiology · 2024Review
- The Role of Neuroglial Metabotropic Glutamate Receptors in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Localization and expression of the Mas-related G-protein coupled receptor member D (MrgD) in the mouse brain.Heliyon · 2021Article
- Regulation and functional consequences of mGluRNA (New York, N.Y.) · 2021Article
- Glucocorticosteroids Effects on Brain Development in the Preterm Infant: A Role for Microglia?Current neuropharmacology · 2021Review
- Putative mGluR4 positive allosteric modulators activate GNeurochemistry international · 2020Article
- Synthesis and Characterization of Fluorine-18-LabeledJournal of medicinal chemistry · 2020Article
- Identification of Compounds With Glucocorticoid Sparing Effects on Suppression of Chemokine and Cytokine Production by Rheumatoid Arthritis Fibroblast-Like Synoviocytes.Frontiers in pharmacology · 2020Article
- Review
- Glutamatergic mechanisms in L-DOPA-induced dyskinesia and therapeutic implications.Journal of neural transmission (Vienna, Austria : 1996) · 2018Article
- Emerging Trends in Pain Modulation by Metabotropic Glutamate Receptors.Frontiers in molecular neuroscience · 2018Review
- Metabotropic Glutamate Receptors in Glial Cells: A New Potential Target for Neuroprotection?Frontiers in molecular neuroscience · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
While the specific trigger of Parkinson Disease (PD) in most patients is unknown, considerable evidence suggests that the neuroinflammatory response makes an essential contribution to the neurodegenerative process. Drugs targeting metabotropic glutamate receptors (mGlu receptors), 7 Transmembrane (7TM) spanning/G protein coupled receptors that bind glutamate, are emerging as therapeutic targets for PD and may have anti-inflammatory properties. ADX88178 is novel potent, selective, and brain-penetrant positive allosteric modulator of the mGlu4 which is under evaluation for treatment of PD and other neurological disorders. We used microglia cultured from mouse brain to determine if ADX88178 had direct effects on the inflammatory responses of these cells. We studied both microglia from wild type and Grm4 knock out mice. We found that activation of mGlu4 with ADX88178 attenuated LPS-induced inflammation in primary microglia, leading to a decrease in the expression of TNFα, MHCII, and iNOS, markers of pro-inflammatory responses. These effects were absent in microglia from mice lacking mGlu4. These results demonstrate a cell-autonomous anti-inflammatory effect of ADX88178 mediated mGlu4 activation on microglia, and suggest that this drug or similar activators or potentiators of mGlu4 may have disease-modifying as well as symptomatic effects in PD and other brain disorders with an inflammatory component.
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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.