ReviewFrontiers in neuroscience2015
Chronic Glutamate Toxicity in Neurodegenerative Diseases-What is the Evidence?
Review in Frontiers in neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 364 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
364 citing papers in PubMed, 8 syntheses or guidelines pooled it, 704 citations in OpenAlex.
- Cannabinoids, the Blood-Brain Barrier, and Neurodegeneration: Mechanisms, Dysregulation, and Therapeutic Perspectives.Biomolecules · 2026Pooled it
- L-Carnitine in the Treatment of Psychiatric and Neurological Manifestations: A Systematic Review.Nutrients · 2024Pooled it
- The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review.Nutrients · 2024Pooled it
- A quantitative meta-analysis of vitamin C in the pathophysiology of Alzheimer's disease.Frontiers in aging neuroscience · 2022Pooled it
- Effect of ouabain on calcium signaling in rodent brain: A systematic review ofFrontiers in pharmacology · 2022Pooled it
- Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?-A Systematic Review.International journal of molecular sciences · 2021Pooled it
- The Efficacy of Ketogenic Therapies in the Clinical Management of People with Neurodegenerative Disease: A Systematic Review.Advances in nutrition (Bethesda, Md.) · 2021Pooled it
- Pooled it
- Structural compression and entorhinal vulnerability: Linking tentorial adjacency to tau burden and dementia progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Total saponins fromJournal of ginseng research · 2026Article
- Potential of intranasal caffeine as a delivery route for treating glutamate-linked hippocampal neurodegeneration by activating endogenous antioxidant defenses.Molecular biology reports · 2026Article
- Cortical-Hypothalamic Assembloids Uncover the Cortical Regulation of Hypothalamic Responses to Fatty Acid.Cell proliferation · 2026Article
- 5T-Based Glutamate Chemical Exchange Saturation Transfer Imaging for Adult Diffuse Glioma Stratification.Journal of magnetic resonance imaging : JMRI · 2026Article
- Untargeted Metabolomic Signature of Mice with Ischemic Stroke.Metabolites · 2026Article
- Resorcinol and Related Simple Phenolic Compounds Increase Astrocyte Survival in a Glutamate-Induced Excitotoxicity Model.Journal of xenobiotics · 2026Article
- Single-nucleus multiome shows motor neuron glutamate overactivation in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- The Glutamate-Glutathione axis in neuropsychiatric disorders and cancer: From shared mechanisms to non-invasive biomarkers.Redox biology · 2026Review
- Mercury-induced excitotoxicity in autism spectrum disorder: disruption of glutamatergic homeostasis and the therapeutic role of the selenium-glutathione axis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Role of dysregulated calcium homeostasis in astrocytes in neurodegenerative disorders.Nature reviews. Neuroscience · 2026Review
- Direct mapping of neural activity via glutamate-weighted magnetic resonance imaging.Innovation (Cambridge (Mass.)) · 2026Article
304 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
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Together with aspartate, glutamate is the major excitatory neurotransmitter in the brain. Glutamate binds and activates both ligand-gated ion channels (ionotropic glutamate receptors) and a class of G-protein coupled receptors (metabotropic glutamate receptors). Although the intracellular glutamate concentration in the brain is in the millimolar range, the extracellular glutamate concentration is kept in the low micromolar range by the action of excitatory amino acid transporters that import glutamate and aspartate into astrocytes and neurons. Excess extracellular glutamate may lead to excitotoxicity in vitro and in vivo in acute insults like ischemic stroke via the overactivation of ionotropic glutamate receptors. In addition, chronic excitotoxicity has been hypothesized to play a role in numerous neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. Based on this hypothesis, a good deal of effort has been devoted to develop and test drugs that either inhibit glutamate receptors or decrease extracellular glutamate. In this review, we provide an overview of the different pathways that are thought to lead to an over-activation of the glutamatergic system and glutamate toxicity in neurodegeneration. In addition, we summarize the available experimental evidence for glutamate toxicity in animal models of neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.