ArticleNeuropharmacology2014
Different oxysterols have opposing actions at N-methyl-D-aspartate receptors.
Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 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.
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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
57 citing papers in PubMed, 83 citations in OpenAlex.
- Structure-activity relationships of steroid and sterol neuromodulators on inflammatory markers in a murine microglial cell line.The Journal of steroid biochemistry and molecular biology · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- Aging and Corneal Nerve Health: Mechanisms of Degeneration and Emerging Therapies for the Cornea.Cells · 2025Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- 25-Hydroxycholesterol as a negative regulator of diaphragm muscle contractions via estrogen receptor and CaHistochemistry and cell biology · 2025Article
- Effects of acute pro-inflammatory stimulation and 25-hydroxycholesterol on hippocampal plasticity and learning involve NLRP3 inflammasome and cellular stress responses.Scientific reports · 2025Article
- Role of cholesterol in modulating brain hyperexcitability.Epilepsia · 2025Review
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- Effects of Complete and Partial Loss of the 24S-Hydroxycholesterol-Generating EnzymeBiomolecules · 2024Article
- 24S-Hydroxycholesterol in Neuropsychiatric Diseases: Schizophrenia, Autism Spectrum Disorder, and Bipolar Disorder.Advances in experimental medicine and biology · 2024Article
- Oxysterols in Central and Peripheral Synaptic Communication.Advances in experimental medicine and biology · 2024Article
- Article
- Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina.Neural regeneration research · 2023Review
- 24-Hydroxycholesterol Induces Tau Proteasome-Dependent Degradation via the SIRT1/PGC1α/Nrf2 Pathway: A Potential Mechanism to Counteract Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2023Article
- Lipids in major depressive disorder: new kids on the block or old friends revisited?Frontiers in psychiatry · 2023Review
- 25-Hydroxycholesterol as a Signaling Molecule of the Nervous System.Biochemistry. Biokhimiia · 2022Review
- Review
- Medication effects on developmental sterol biosynthesis.Molecular psychiatry · 2022Review
- Cholesterol in Brain Development and Perinatal Brain Injury: More than a Building Block.Current neuropharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Oxysterols have emerged as important biomarkers in disease and as signaling molecules. We recently showed that the oxysterol 24(S)-hydroxycholesterol, the major brain cholesterol metabolite, potently and selectively enhances NMDA receptor function at a site distinct from other modulators. Here we further characterize the pharmacological mechanisms of 24(S)-hydroxycholesterol and its synthetic analog SGE201. We describe an oxysterol antagonist of this positive allosteric modulation, 25-hydroxycholesterol. We found that 24(S)-hydroxycholesterol and SGE201 primarily increased the efficacy of NMDAR agonists but did not directly gate the channel or increase functional receptor number. Rather than binding to a direct aqueous-accessible site, oxysterols may partition into the plasma membrane to access the NMDAR, likely explaining slow onset and offset kinetics of modulation. Interestingly, oxysterols were ineffective when applied to the cytosolic face of inside-out membrane patches or through a whole-cell pipette solution, suggesting a non-intracellular site. We also found that another natural oxysterol, 25-hydroxycholesterol, although exhibiting slight potentiation on its own, non-competitively and enantioselectively antagonized the effects of 24(S)-hydroxycholesterol analogs. In summary, we suggest two novel allosteric sites on NMDARs that separately modulate channel gating, but together oppose each other.
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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.