ArticlePloS one2012
Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid and H2O2-induced stress.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis 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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Glutamatergic and GABAergic metabolite levels in Alzheimer's disease: a systematic review and meta-analysis.BMC neurology · 2025Pooled it
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- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders.BMC medicine · 2025Article
- Clostridioides difficile Infection in Aged Mice Decreases Memory Function, Which Can Be Protected with Alanyl-Glutamine Supplementation.The Journal of nutrition · 2025Article
- Investigating the neuroprotective effects ofHeliyon · 2025Article
- Mitochondrial bioenergetics stimulates autophagy for pathological MAPT/Tau clearance in tauopathy neurons.Autophagy · 2025Article
- CSF amino acid profiles in ICV-streptozotocin-induced sporadic Alzheimer's disease in male Wistar rat: a metabolomics and systems biology perspective.FEBS open bio · 2024Article
- In vitro heterochronic parabiosis identifies pigment epithelium-derived factor as a systemic mediator of rejuvenation by young blood.bioRxiv : the preprint server for biology · 2024Article
- Mendelian Randomization of Blood Metabolites Suggests Circulating Glutamine Protects Against Late-Onset Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders.Molecular psychiatry · 2023Article
- Sting and p53 DNA repair pathways are compromised in Alzheimer's disease.Scientific reports · 2023Article
- Circular RNA Tmcc1 improves astrocytic glutamate metabolism and spatial memory via NF-κB and CREB signaling in a bile duct ligation mouse model: transcriptional and cellular analyses.Journal of neuroinflammation · 2023Article
- Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer's disease: a cross-sectional metabolomic analysis.Frontiers in aging neuroscience · 2023Article
- Bioenhancing effects of piperine and curcumin on triterpenoid pharmacokinetics and neurodegenerative metabolomes from Centella asiatica extract in beagle dogs.Scientific reports · 2022Article
- Article
- Müller cell degeneration and microglial dysfunction in the Alzheimer's retina.Acta neuropathologica communications · 2022Article
- Protective Effect of Low Dose of Methamphetamine on The Amount of Extracellular Glutamine in Primary Fetal Human Astrocytes Induced by Amyloid Beta.Cell journal · 2022Article
- Glutamine Availability Regulates the Development of Aging Mediated by mTOR Signaling and Autophagy.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glutamine is the most abundant free amino acid in the human blood stream and is 'conditionally essential' to cells. Its intracellular levels are regulated both by the uptake of extracellular glutamine via specific transport systems and by its intracellular synthesis by glutamine synthetase (GS). Adding to the regulatory complexity, when extracellular glutamine is reduced GS protein levels rise. Unfortunately, this excess GS can be maladaptive. GS overexpression is neurotoxic especially if the cells are in a low-glutamine medium. Similarly, in low glutamine, the levels of multiple stress response proteins are reduced rendering cells hypersensitive to H(2)O(2), zinc salts and DNA damage. These altered responses may have particular relevance to neurodegenerative diseases of aging. GS activity and glutamine levels are lower in the Alzheimer's disease (AD) brain, and a fraction of AD hippocampal neurons have dramatically increased GS levels compared with control subjects. We validated the importance of these observations by showing that raising glutamine levels in the medium protects cultured neuronal cells against the amyloid peptide, Aβ. Further, a 10-day course of dietary glutamine supplementation reduced inflammation-induced neuronal cell cycle activation, tau phosphorylation and ATM-activation in two different mouse models of familial AD while raising the levels of two synaptic proteins, VAMP2 and synaptophysin. Together, our observations suggest that healthy neuronal cells require both intracellular and extracellular glutamine, and that the neuroprotective effects of glutamine supplementation may prove beneficial in the treatment of AD.
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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.