ArticleProceedings of the National Academy of Sciences of the United States of America2000
D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 435 papers, 2 of them syntheses that pooled it.
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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
435 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,122 citations in OpenAlex.
- The glutamatergic system in Alzheimer's disease: a systematic review with meta-analysis.Molecular psychiatry · 2024Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- The D-amino acid oxidase inhibitor luvadaxistat improves mismatch negativity in patients with schizophrenia in a randomized trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Trial
- BCG vaccination mitigates tau pathology and restores cognitive function in PS19 mice.Science advances · 2026Article
- A thioredoxin-Serinc2-lipid signaling axis modulates mood-related behaviors in mice.Molecular psychiatry · 2026Article
- Substrate recognition and transport mechanism of the human proton-coupled amino-acid transporter 1 (SLC36A1).Nature communications · 2026Article
- Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.APL bioengineering · 2026Review
- Blood levels of D-aspartate oxidase, D-amino acid oxidase, serine racemase, and pLG72 are influenced by diagnoses of schizophrenia and autism spectrum disorder.Schizophrenia (Heidelberg, Germany) · 2026Article
- Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer's and wild-type mice.Scientific reports · 2026Article
- Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes.Brain : a journal of neurology · 2026Article
- Microglial serine racemase knockout alleviates Alzheimer-like neuropathology and behavioral deficit via lactylation-mediated anti-inflammation.Communications biology · 2026Article
- D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.Cellular and molecular neurobiology · 2026Review
- Junctional conductance of retinal AII amacrine cell electrical synapses is decreased by NMDA receptors.The Journal of physiology · 2026Article
- Blood-Based Metabolomic Biomarkers and Personality Traits in Major Depressive Disorder: Toward an Integrated Framework for Precision Psychiatry.Advances in experimental medicine and biology · 2026Review
- D-serine supplementation is associated with mucosal-prioritized rumen development and propionate-enriched fermentation with selective microbial shifts in pre-weaning Hu lambs.Frontiers in microbiology · 2026Article
- From bugs to behavior: targeting the gut-brain interface for addiction therapeutics.Gut microbes · 2025Review
- Galectin-related protein, a key contributor, drives diabetes-associated neuropathic pain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Low-dose mixtures of dietary nutrients ameliorate behavioral deficits in multiple mouse models of autism.PLoS biology · 2025Article
- D-Serine's Journey Between Stars and Synapses.Neurochemical research · 2025Review
- Astrocytic dopamine D1 receptor modulates glutamatergic transmission and synaptic plasticity in the prefrontal cortex through d-serine.Acta pharmaceutica Sinica. B · 2025Article
375 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
8 authors at 3 institutions in 1 country.
Funding
Abstract
Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of d-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied D-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses.
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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.