ArticleThe Journal of clinical investigation2014
Small-molecule activator of glutamate transporter EAAT2 translation provides neuroprotection.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- EAAT2 as a therapeutic research target in Alzheimer's disease: A systematic review.Frontiers in neuroscience · 2022Pooled it
- Astrocytes in Neurodegeneration: Spatial States, Crosstalk, and Emerging Therapies.Molecular neurobiology · 2026Review
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Multi-Target Neuroprotective Compound Exhibits EAAT2-Modulating and Alzheimer's Pathology-Attenuating Effects in In Vitro and In Vivo Models.ACS chemical neuroscience · 2026Article
- Glutamate transmission in the prelimbic cortex and nucleus accumbens shell is involved in ethanol reinforcement and drinking in rats.Frontiers in behavioral neuroscience · 2026Article
- Pigment Epithelium-Derived Factor Deficiency Impairs Hippocampal Glutamate Homeostasis and Cognitive Function by Downregulating Astrocytic GLT-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Medical and Nonmedical Applications of Synthetic Transmembrane Anion Transporters.Chemical reviews · 2025Review
- The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.Immunity · 2025Article
- Exposure to polystyrene nanoplastics causes anxiety and depressive-like behavior and down-regulates EAAT2 expression in mice.Archives of toxicology · 2025Article
- EAAT2 Activation Regulates Glutamate Excitotoxicity and Reduces Impulsivity in a Rodent Model of Parkinson's Disease.Molecular neurobiology · 2025Article
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- The kinase LRRK2 is required for the physiological function and expression of the glial glutamate transporter EAAT2 (SLC1A2).Journal of neurochemistry · 2025Article
- An unrecognized mechanism of self-protection in degenerating neurons mediated by astrocytic YAP through Wnts/β-catenin/EAAT2 signaling in C9orf72-poly-GA mice.Theranostics · 2025Article
- Article
- Distinct forebrain regions define a dichotomous astrocytic profile in multiple system atrophy.Acta neuropathologica communications · 2024Article
- The m6A reader YTHDC2 promotes the pathophysiology of temporal lobe epilepsy by modulating SLC7A11-dependent glutamate dysregulation in astrocytes.Theranostics · 2024Article
- Neuronal MML-1/MXL-2 regulates systemic aging via glutamate transporter and cell nonautonomous autophagic and peroxidase activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans.Psychopharmacology · 2023Review
- The Amyloid Cascade Hypothesis in Alzheimer's Disease: Should We Change Our Thinking?Biomolecules · 2023Review
- A Medicinal Chemistry Perspective on Excitatory Amino Acid Transporter 2 Dysfunction in Neurodegenerative Diseases.Journal of medicinal chemistry · 2023Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Glial glutamate transporter EAAT2 plays a major role in glutamate clearance in synaptic clefts. Several lines of evidence indicate that strategies designed to increase EAAT2 expression have potential for preventing excitotoxicity, which contributes to neuronal injury and death in neurodegenerative diseases. We previously discovered several classes of compounds that can increase EAAT2 expression through translational activation. Here, we present efficacy studies of the compound LDN/OSU-0212320, which is a pyridazine derivative from one of our lead series. In a murine model, LDN/OSU-0212320 had good potency, adequate pharmacokinetic properties, no observed toxicity at the doses examined, and low side effect/toxicity potential. Additionally, LDN/OSU-0212320 protected cultured neurons from glutamate-mediated excitotoxic injury and death via EAAT2 activation. Importantly, LDN/OSU-0212320 markedly delayed motor function decline and extended lifespan in an animal model of amyotrophic lateral sclerosis (ALS). We also found that LDN/OSU-0212320 substantially reduced mortality, neuronal death, and spontaneous recurrent seizures in a pilocarpine-induced temporal lobe epilepsy model. Moreover, our study demonstrated that LDN/OSU-0212320 treatment results in activation of PKC and subsequent Y-box-binding protein 1 (YB-1) activation, which regulates activation of EAAT2 translation. Our data indicate that the use of small molecules to enhance EAAT2 translation may be a therapeutic strategy for the treatment of neurodegenerative diseases.
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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.