ArticleAntioxidants & redox signaling2010
Delineating the role of glutathione peroxidase 4 in protecting cells against lipid hydroperoxide damage and in Alzheimer's disease.
Article in Antioxidants & redox signaling, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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Who cites it
69 citing papers in PubMed, 148 citations in OpenAlex.
- Ferroptosis and aging: Inducing and catalyzing neurodegenerative diseases.Neural regeneration research · 2026Article
- Ferroptosis in neurological diseases: moving towards therapeutic intervention.Molecular psychiatry · 2026Review
- Sevoflurane-induced ferroptosis in developing neurons mediated by the NCOA4-ferritinophagy-GPX4 pathway.Journal of molecular histology · 2026Article
- Ferroptosis and Alzheimer's disease: a new insight into neurodegeneration.Frontiers in immunology · 2026Review
- Regulating Ferroptosis in Leukemic Stem Cells: From Stemness Preservation to Targeted Differentiation Strategies.Stem cell reviews and reports · 2026Review
- PINK1-dependent NFKB signaling contributes to amyloid pathology in Alzheimer disease.Autophagy · 2025Article
- Review
- Ferroptosis and Alzheimer's: unveiling new avenues for the treatment and prevention.Metabolic brain disease · 2025Review
- Beyond oxidative stress: Ferroptosis as a novel orchestrator in neurodegenerative disorders.Frontiers in immunology · 2025Review
- Ferroptosis in central nervous system injuries: molecular mechanisms, diagnostic approaches, and therapeutic strategies.Frontiers in cellular neuroscience · 2025Review
- New horizons for the role of selenium on cognitive function: advances and challenges.Metabolic brain disease · 2024Review
- Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.Archives of toxicology · 2024Review
- Oxytosis/Ferroptosis in Neurodegeneration: the Underlying Role of Master Regulator Glutathione Peroxidase 4 (GPX4).Molecular neurobiology · 2024Review
- Ferroptosis inhibitors: past, present and future.Frontiers in pharmacology · 2024Review
- Review
- Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.Frontiers in cellular neuroscience · 2024Review
- Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- American Ginseng for the Treatment of Alzheimer's Disease: A Review.Molecules (Basel, Switzerland) · 2023Review
- Selenium and Selenoproteins in Health.Biomolecules · 2023Review
- GPX4 deficiency-dependent phospholipid peroxidation drives motor deficits of ALS.Journal of advanced research · 2023Article
9 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
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Numerous studies characterizing the function of glutathione peroxidase 4 (GPx4) have demonstrated that this selenoenzyme is protective against oxidative stress. Herein, we characterized the function of this protein by targeting GPx4 downregulation using RNA interference. Partial knockdown of GPx4 levels resulted in growth retardation and morphological changes. Surprisingly, GPx4 knockdown cells showed virtually unchanged levels of intracellular ROS, yet highly increased levels of oxidized lipid by-products. GPx1, another glutathione peroxidase and a major cellular peroxide scavenging enzyme, did not rescue GPx4-deficient cells and did not reduce lipid peroxide levels. The data established an essential role of GPx4 in protecting cells against lipid hydroperoxide damage, yet a limited role as a general antioxidant enzyme. As oxidized lipid hydroperoxides are a characteristic of neurodegenerative diseases, we analyzed brain tissues of mice suffering from a model of Alzheimer's disease and found that oxidized lipid by-products were enriched, and expression of both GPx4 and guanine-rich sequence-binding factor, which is known to control GPx4 synthesis, was downregulated. Brain tissue from an Alzheimer's diseased human also manifested enhanced levels of one of the oxidized lipid by-products, 4-hydroxynonenal. These data suggest a role of GPx4 in neurodegenerative diseases through its function in removal of lipid hydroperoxides.
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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.