ArticleNeurochemical research2017
NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.
Article in Neurochemical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Toothache and Alzheimer's Disease: A Mendelian Randomization Study of the NAAG-CD33 Neuroimmune Axis.Journal of pain research · 2026Article
- Targeting NAAG metabolism restores cognition and synaptic integrity in EcoHIV-infected mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Post-methamphetamine working memory decline predicts relapse vulnerability in rats and is rescued by mGlu3 receptor activation.Psychopharmacology · 2026Article
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Mass spectrometry-guided discovery of novel GCPII inhibitor scaffolds.Frontiers in pharmacology · 2025Article
- Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression withNeurobiology of aging · 2024Article
- Effects of systemic pretreatment with the NAALADase inhibitor 2-PMPA on oral methamphetamine reinforcement in C57BL/6J mice.Frontiers in psychiatry · 2024Article
- 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
- Metabotropic glutamate receptor 3 as a potential therapeutic target for psychiatric and neurological disorders.Pharmacology, biochemistry, and behavior · 2022Review
- Inhibition of glutamate-carboxypeptidase-II in dorsolateral prefrontal cortex: potential therapeutic target for neuroinflammatory cognitive disorders.Molecular psychiatry · 2022Article
- Review
- Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects.Frontiers in chemistry · 2022Review
- Ceftriaxone Suppresses Group II Metabotropic Glutamate Receptor Expression Contributing to Reversal of Recognition Memory Deficits of Amyloid Precursor Protein/Presenilin 1 AD Mice.Frontiers in neuroscience · 2022Article
- Evidence of NAAG-family tripeptide NAAGJournal of neurochemistry · 2021Article
- Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance.Frontiers in aging neuroscience · 2021Article
- The Dual Role of Glutamatergic Neurotransmission in Alzheimer's Disease: From Pathophysiology to Pharmacotherapy.International journal of molecular sciences · 2020Review
- Amygdala group II mGluRs mediate the inhibitory effects of systemic group II mGluR activation on behavior and spinal neurons in a rat model of arthritis pain.Neuropharmacology · 2019Article
- A role for N-acetylaspartylglutamate (NAAG) and mGluR3 in cognition.Neurobiology of learning and memory · 2019Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.
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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.