ArticleScientific reports2015
Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 52 citations in OpenAlex.
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Natural aminosterols inhibit NMDA receptors with low nanomolar potency.The FEBS journal · 2025Article
- Inhibition of NMDA receptors and other ion channel types by membrane-associated drugs.Frontiers in pharmacology · 2025Review
- Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology.Physiological research · 2024Review
- Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.Cellular and molecular life sciences : CMLS · 2024Article
- Structural insights into opposing actions of neurosteroids on GABANature communications · 2023Article
- Novel neurosteroid pregnanolone pyroglutamate suppresses neurotoxicity syndrome induced by tetramethylenedisulfotetramine but is ineffective in a rodent model of infantile spasms.Pharmacological reports : PR · 2023Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor.Biomolecules · 2021Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Pitfalls of NMDA Receptor Modulation by Neuroactive Steroids. The Effect of Positive and Negative Modulation of NMDA Receptors in an Animal Model of Schizophrenia.Biomolecules · 2021Article
- Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease.Essays in biochemistry · 2020Review
- Site of Action of Brain Neurosteroid Pregnenolone Sulfate at the N-Methyl-D-Aspartate Receptor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- NMDA Receptor Opening and Closing-Transitions of a Molecular Machine Revealed by Molecular Dynamics.Biomolecules · 2019Article
- Positive and Negative Allosteric Modulators of N-Methyl-d-aspartate (NMDA) Receptors: Structure-Activity Relationships and Mechanisms of Action.Journal of medicinal chemistry · 2019Review
- Structure, function, and allosteric modulation of NMDA receptors.The Journal of general physiology · 2018Review
- Article
- Strong Inhibitory Effect, Low Cytotoxicity and High Plasma Stability of Steroidal Inhibitors ofFrontiers in pharmacology · 2018Article
- The LILI Motif of M3-S2 Linkers Is a Component of the NMDA Receptor Channel Gate.Frontiers in molecular neuroscience · 2018Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system.
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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.