ArticleThe Journal of biological chemistry2015
Ablation of the Ferroptosis Inhibitor Glutathione Peroxidase 4 in Neurons Results in Rapid Motor Neuron Degeneration and Paralysis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 279 papers, 2 of them syntheses that pooled it.
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Who cites it
279 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Bibliometric analysis of cognitive dysfunction after traumatic brain injury.Frontiers in neuroscience · 2025Pooled it
- The molecular mechanism of ferroptosis and its role in COPD.Frontiers in medicine · 2022Pooled it
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- Atractylenolide I stabilizes HMOX1 to induce ferroptosis and enhance lenvatinib efficacy in hepatocellular carcinoma.iScience · 2026Article
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Cysteine metabolism dysregulation promotes ferroptosis in osteoarthritis: Insights from multi-species bioinformatics and experimental validation.Journal of orthopaedic translation · 2026Article
- Regulation of lipid oxidation and ferroptosis by a tunable axis of vitamin E, high-density lipoprotein, and scavenger receptor class B type 1.The Journal of biological chemistry · 2026Article
- Amyloid-β aggregates induce vasculopathy via ferroptosis in brain endothelial cells.Brain pathology (Zurich, Switzerland) · 2026Article
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Predominance of Ferroptotic Cell Death Mechanisms in Substantia Nigra Neurodegeneration in Parkinson's Disease.Annals of neurology · 2026Article
- The role of autophagy in spinal cord injury: Mechanisms, crosstalk, and therapeutic strategies.Neural regeneration research · 2026Article
- Differential expression of ALOX15 and GPX4 in the testicular tissue of men with obstructive and non-obstructive azoospermia: a cross-sectional study.Translational andrology and urology · 2026Article
- Deuterated polyunsaturated fatty acids alleviate in vitro skeletal muscle dysfunction induced by oxidative stress.Free radical biology & medicine · 2026Article
- Article
- Mechanism of L-Buthionine-(S,R)-sulfoximine-induced ferroptotic cell death in mouse hippocampal neuronal cells.Cell communication and signaling : CCS · 2026Article
- miR-24-3p promotes spinal cord injury repair in rats by inhibiting ferroptosisNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Gambogic acid-loaded transferrin-modified liposomes enhancing potent ferroptosis in breast cancer.Scientific reports · 2026Article
- Acidosis, Iron Dyshomeostasis and Inflammatory Injury.International journal of molecular sciences · 2026Review
- Ferroptotic neurodegeneration and diet: a narrative review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Genetics of selenoproteins and selenoprotein metabolism - An overview of current concepts and emerging aspects.Redox biology · 2026Review
219 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Glutathione peroxidase 4 (GPX4), an antioxidant defense enzyme active in repairing oxidative damage to lipids, is a key inhibitor of ferroptosis, a non-apoptotic form of cell death involving lipid reactive oxygen species. Here we show that GPX4 is essential for motor neuron health and survival in vivo. Conditional ablation of Gpx4 in neurons of adult mice resulted in rapid onset and progression of paralysis and death. Pathological inspection revealed that the paralyzed mice had a dramatic degeneration of motor neurons in the spinal cord but had no overt neuron degeneration in the cerebral cortex. Consistent with the role of GPX4 as a ferroptosis inhibitor, spinal motor neuron degeneration induced by Gpx4 ablation exhibited features of ferroptosis, including no caspase-3 activation, no TUNEL staining, activation of ERKs, and elevated spinal inflammation. Supplementation with vitamin E, another inhibitor of ferroptosis, delayed the onset of paralysis and death induced by Gpx4 ablation. Also, lipid peroxidation and mitochondrial dysfunction appeared to be involved in ferroptosis of motor neurons induced by Gpx4 ablation. Taken together, the dramatic motor neuron degeneration and paralysis induced by Gpx4 ablation suggest that ferroptosis inhibition by GPX4 is essential for motor neuron health and survival in vivo.
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