ArticleProceedings of the National Academy of Sciences of the United States of America2012
Inhibition of glutamate carboxypeptidase II (GCPII) activity as a treatment for cognitive impairment in multiple sclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Prostate-Specific Membrane Antigen as Target for Neuroimaging of Central Nervous System Tumors.Molecular imaging · 2022Pooled it
- Glutamate carboxypeptidase II activation in astrocytes mediates glymphatic impairment and cognitive vulnerability in the aging brain following surgery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Modulating glutamate neurotransmission inFrontiers in immunology · 2026Review
- Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.Psychopharmacology · 2026Article
- Targeting NAAG metabolism restores cognition and synaptic integrity in EcoHIV-infected mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasis.Nature communications · 2025Article
- Article
- PROTAC technology for prostate cancer treatment.Acta materia medica · 2025Article
- Mass spectrometry-guided discovery of novel GCPII inhibitor scaffolds.Frontiers in pharmacology · 2025Article
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer.Nature reviews. Urology · 2025Review
- Effects of radiofrequency field from 5G communication on fecal microbiome and metabolome profiles in mice.Scientific reports · 2024Article
- Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders.Molecular psychiatry · 2023Review
- Dendrimer-enabled targeted delivery attenuates glutamate excitotoxicity and improves motor function in a rabbit model of cerebral palsy.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.Neurology international · 2023Review
- Dendrimer-Conjugated Glutamate Carboxypeptidase II Inhibitor Restores Microglial Changes in a Rabbit Model of Cerebral Palsy.Developmental neuroscience · 2023Article
- Inhibition of glutamate-carboxypeptidase-II in dorsolateral prefrontal cortex: potential therapeutic target for neuroinflammatory cognitive disorders.Molecular psychiatry · 2022Article
- D-DOPA Is a Potent, Orally Bioavailable, Allosteric Inhibitor of Glutamate Carboxypeptidase II.Pharmaceutics · 2022Article
- Characterization of a mGluR5 Knockout Rat Model with Hallmarks of Fragile X Syndrome.Life (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Half of all patients with multiple sclerosis (MS) experience cognitive impairment, for which there is no pharmacological treatment. Using magnetic resonance spectroscopy (MRS), we examined metabolic changes in the hippocampi of MS patients, compared the findings to performance on a neurocognitive test battery, and found that N-acetylaspartylglutamate (NAAG) concentration correlated with cognitive functioning. Specifically, MS patients with cognitive impairment had low hippocampal NAAG levels, whereas those with normal cognition demonstrated higher levels. We then evaluated glutamate carboxypeptidase II (GCPII) inhibitors, known to increase brain NAAG levels, on cognition in the experimental autoimmune encephalomyelitis (EAE) model of MS. Whereas GCPII inhibitor administration did not affect physical disabilities, it increased brain NAAG levels and dramatically improved learning and memory test performance compared with vehicle-treated EAE mice. These data suggest that NAAG is a unique biomarker for cognitive function in MS and that inhibition of GCPII might be a unique therapeutic strategy for recovery of cognitive function.
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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.