ArticleJournal of neuroinflammation2021
Suppression of neuroinflammation by an allosteric agonist and positive allosteric modulator of the α7 nicotinic acetylcholine receptor GAT107.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Neuroprotective activity of the α7-nAChR positive allosteric modulator PNU-120596 on short term outcomes after traumatic brain injury.Experimental neurology · 2026Article
- Alpha-7 nicotinic acetylcholine receptor: targeting the interplay between inflammation, renin-angiotensin aldosterone system, and nervous system for the novel treatment of heart failure.Frontiers in pharmacology · 2026Review
- Structural basis for allosteric agonism of human α7 nicotinic acetylcholine receptors.Cell discovery · 2025Article
- Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions.Frontiers in immunology · 2025Review
- The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic.PloS one · 2025Article
- The role of kynurenines in migraine-related neuroimmune pathways.The journal of headache and pain · 2024Review
- Electrical stimulation of the vagus nerve ameliorates inflammation and disease activity in a rat EAE model of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Basal forebrain cholinergic systems as circuits through which traumatic stress disrupts emotional memory regulation.Neuroscience and biobehavioral reviews · 2024Review
- Activating α7nAChR suppresses systemic inflammation by mitigating neuroinflammation of the medullary visceral zone in sepsis in a rat model.Translational neuroscience · 2024Article
- Neuroimmune nexus in the pathophysiology and therapy of inflammatory disorders: Role of α7 nicotinic acetylcholine receptors.Pharmacological research · 2023Review
- SARS-CoV-2 spike ectodomain targets α7 nicotinic acetylcholine receptors.The Journal of biological chemistry · 2023Article
- Nicotinic acetylcholine receptors: Therapeutic targets for novel ligands to treat pain and inflammation.Pharmacological research · 2023Review
- Cholinergic dysfunction in COVID-19: frantic search and hoping for the best.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Dose-dependent effects of GAT107, a novel allosteric agonist-positive allosteric modulator (ago-PAM) for the α7 nicotinic cholinergic receptor: a BOLD phMRI and connectivity study on awake rats.Frontiers in neuroscience · 2023Article
- Cannabidiol as a modulator of α7 nicotinic receptors.Cellular and molecular life sciences : CMLS · 2022Article
- Nicotinic Acetylcholine Receptors and Microglia as Therapeutic and Imaging Targets in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2022Review
- Bilateral Superior Cervical Sympathectomy Activates Signal Transducer and Activator of Transcription 3 Signal to Alleviate Myocardial Ischemia-Reperfusion Injury.Frontiers in cardiovascular medicine · 2022Article
- The Mechanisms Mediated by α7 Acetylcholine Nicotinic Receptors May Contribute to Peripheral Nerve Regeneration.Molecules (Basel, Switzerland) · 2021Article
- Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases.International journal of molecular sciences · 2021Review
- Neuroinflammation Modulation via α7 Nicotinic Acetylcholine Receptor and Its Chaperone, RIC-3.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe α7 nicotinic acetylcholine receptor (α7 nAChR) negatively regulates the synthesis and release of pro-inflammatory cytokines by immune cells. Our previous studies showed that in encephalitogenic T cells, α7 nAChR expression is upregulated and that activation of the cholinergic system can attenuate experimental autoimmune encephalomyelitis (EAE). GAT107 is an allosteric agonist and positive allosteric modulator (ago-PAM) of α7 nAChR that can produce persistent activation of this receptor. Therefore, in the present study, we investigated the effect of GAT107 on neuroinflammation in EAE, the animal model used for the study of multiple sclerosis (MS) via α7 nAChR, and the inflammatory pathways involved.
methodsEAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG
resultsFollowing activation of the α7 nAChR by GAT107 during EAE, disease severity was significantly reduced by 70% and was correlated with a reduction in the extent of neuroinflammation in the CNS. The treatment reduced encephalitogenic T cell proliferation and the production of pro-inflammatory cytokines, as well as increased the production of the anti-inflammatory cytokine IL-10. Furthermore, the expression of immune cell markers was altered by GAT107 treatment, which induced a significant reduction in macrophages, dendritic cells, and B cells, as well as a reduction in anti-MOG
conclusionsOur results show that GAT107 can be a useful molecule for harnessing the cholinergic anti-inflammatory pathway for long-lasting and wide-ranging modulation and downregulation of neuroinflammation in EAE.
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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.