ArticleNature communications2023
Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Molecular architecture of the fungal-specific potassium channel TOK1.Nature communications · 2026Article
- Auxiliary subunits reshape structural asymmetry and functional plasticity in heterotetrameric GluA1/A2 AMPA receptor core.Nature communications · 2026Article
- Structure and organization of AMPA receptor-TARP complexes in the mammalian cerebellum.Science (New York, N.Y.) · 2026Article
- Auxiliary TARP Subunits Define AMPA Receptor Pharmacology and Function.Journal of xenobiotics · 2026Article
- Efficient and rapid isolation of native AMPA receptor complexes for cryo-EM.Protein science : a publication of the Protein Society · 2026Article
- JNJ-55511118 Stabilizes a Desensitized-like Conformation of γ8-Containing AMPA Receptors through Long-Range Allosteric Modulation.bioRxiv : the preprint server for biology · 2025Article
- Atomistic mechanisms of calcium permeation modulated by Q/R editing and selectivity filter mutations in GluA2 AMPA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Memantine inhibits calcium-permeable AMPA receptors.Nature communications · 2025Article
- Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today.Pharmacology, biochemistry, and behavior · 2025Review
- Structure of transmembrane AMPA receptor regulatory protein subunit γ2.Nature communications · 2025Article
- Pharmacological modulation of respiratory control: Ampakines as a therapeutic strategy.Pharmacology & therapeutics · 2025Review
- Allosteric competition and inhibition in AMPA receptors.Nature structural & molecular biology · 2024Article
- Exploring the impact of the stargazin V143L mutation on the dynamics of the AMPA receptor: stargazin complex.Frontiers in cellular neuroscience · 2024Article
- Roles of AMPA receptors in social behaviors.Frontiers in synaptic neuroscience · 2024Review
- Potentiation of AMPA receptors for rapid therapeutic gain in psychiatry has reached a new level of excitement.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Structure of Transmembrane AMPA Receptor Regulatory Protein Subunit γ2.bioRxiv : the preprint server for biology · 2023Article
- Allosteric Competition and Inhibition in AMPA Receptors.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three potent, chemically diverse ligands. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we also demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators.
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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.