ArticleThe EMBO journal2011
Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
What it found
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Who cites it
93 citing papers in PubMed, 165 citations in OpenAlex.
- High Plasma Polyamine Levels Are Associated With an Increased Risk of Poststroke Cognitive Impairment: A Multicenter Prospective Study From CATIS.Journal of the American Heart Association · 2025Trial
- GluN2B-specific NMDAR positive allosteric modulation reverses cognitive and behavioral abnormalities inScience advances · 2026Article
- Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026Article
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Article
- Optochemical profiling of NMDAR molecular diversity at synaptic and extrasynaptic sites.The EMBO journal · 2025Article
- Natural aminosterols inhibit NMDA receptors with low nanomolar potency.The FEBS journal · 2025Article
- Spermidine Treatment Improves GRIN2B Loss-Of-Function, A Primary Disorder of Glutamatergic Neurotransmission.Journal of inherited metabolic disease · 2025Article
- A genetically encoded secreted toxin potentiates synaptic NMDA receptors in hippocampal neurons and confers neuroprotection.PNAS nexus · 2025Article
- EAR-20 peptide, a novel NMDA receptor positive allosteric modulator.Frontiers in pharmacology · 2025Article
- Reversible Control of Native GluN2B-Containing NMDA Receptors with Visible Light.ACS chemical neuroscience · 2024Article
- Article
- Rescuing tri-heteromeric NMDA receptor function: the potential of pregnenolone-sulfate in loss-of-function GRIN2B variants.Cellular and molecular life sciences : CMLS · 2024Article
- Polyamines: Key Players in Immunometabolism and Immune Regulation.Journal of cellular immunology · 2024Article
- Downstream Allosteric Modulation of NMDA Receptors by 3-Benzazepine Derivatives.Molecular neurobiology · 2023Article
- GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Structural insights into NMDA receptor pharmacology.Biochemical Society transactions · 2023Review
- Molecular targets of spermidine: implications for cancer suppression.Cell stress · 2023Article
- Pharmacological Potential of 3-Benzazepines in NMDAR-Linked Pathophysiological Processes.Biomedicines · 2023Review
- N-methyl-D-aspartate receptor hypofunction as a potential contributor to the progression and manifestation of many neurological disorders.Frontiers in molecular neuroscience · 2023Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands. While much has been learned recently regarding allosteric inhibition of NMDARs, the structural determinants underlying positive allosteric modulation of these receptors remain poorly defined. Here, we show that polyamines, naturally occurring polycations that selectively enhance NMDARs containing the GluN2B subunit, bind at a dimer interface between GluN1 and GluN2B subunit N-terminal domains (NTDs). Polyamines act by shielding negative charges present on GluN1 and GluN2B NTD lower lobes, allowing their close apposition, an effect that in turn prevents NTD clamshell closure. Our work reveals the mechanistic basis for positive allosteric modulation of NMDARs. It provides the first example of an intersubunit binding site in this class of receptors, a discovery that holds promise for future drug interventions.
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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.