ArticleNature communications2014
Cellular protection using Flt3 and PI3Kα inhibitors demonstrates multiple mechanisms of oxidative glutamate toxicity.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
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Who cites it
80 citing papers in PubMed, 125 citations in OpenAlex.
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- Neutrophil heterogeneity and plasticity: unveiling the multifaceted roles in health and disease.MedComm · 2025Review
- VPS35 D620N mutation impairs neurogenesis and promotes ferroptosis in Parkinson's disease by using molecular docking, molecular dynamic simulation, and cellular model.Frontiers in aging neuroscience · 2025Article
- Identification of RN7SK LncRNA as a novel biomarker in Alzheimer's disease using bioinformatics and expression analysis.Scientific reports · 2024Article
- Neuroprotective Effects of Ethanol ExtractInternational journal of molecular sciences · 2024Article
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- Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Pathological Interplay between Inflammation and Mitochondria Aggravates Glutamate Toxicity.International journal of molecular sciences · 2024Review
- Ion channels in acinar cells in acute pancreatitis: crosstalk of calcium, iron, and copper signals.Frontiers in immunology · 2024Review
- Anthocyanins: Molecular Aspects on Their Neuroprotective Activity.Biomolecules · 2023Review
- The mechanism of ferroptosis and its related diseases.Molecular biomedicine · 2023Review
- Identifying the potential genes in alpha synuclein driving ferroptosis of Parkinson's disease.Scientific reports · 2023Article
- Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage.International journal of molecular sciences · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Glutamate-induced oxidative stress is a major contributor to neurodegenerative diseases. Here, we identify small-molecule inhibitors of this process. We screen a kinase inhibitor library on neuronal cells and identify Flt3 and PI3Kα inhibitors as potent protectors against glutamate toxicity. Both inhibitors prevented reactive oxygen species (ROS) generation, mitochondrial hyperpolarization and lipid peroxidation in neuronal cells, but they do so by distinct molecular mechanisms. The PI3Kα inhibitor protects cells by inducing partial restoration of depleted glutathione levels and accumulation of intracellular amino acids, whereas the Flt3 inhibitor prevents lipid peroxidation, a key mechanism of glutamate-mediated toxicity. We also demonstrate that glutamate toxicity involves a combination of ferroptosis, necrosis and AIF-dependent apoptosis. We confirm the protective effect by using multiple inhibitors of these kinases and multiple cell types. Our results not only identify compounds that protect against glutamate-stimulated oxidative stress, but also provide new insights into the mechanisms of glutamate toxicity in neurons.
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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.