ArticleProceedings of the National Academy of Sciences of the United States of America2015
NADPH oxidase 4 is a critical mediator in Ataxia telangiectasia disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia.Nature communications · 2025Article
- Unraveling the nexus: Genomic instability and metabolism in cancer.Cell reports · 2025Review
- Pioglitazone as a Possible Treatment forBiomolecules · 2024Review
- Metabolism-focused CRISPR screen unveils mitochondrial pyruvate carrier 1 as a critical driver for PARP inhibitor resistance in lung cancer.Molecular carcinogenesis · 2024Article
- CRISPR metabolic screen identifies ATM and KEAP1 as targetable genetic vulnerabilities in solid tumors.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Impact of Oxidative Stress on Pediatrics Syndromes.Antioxidants (Basel, Switzerland) · 2022Review
- ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors.International journal of molecular sciences · 2022Review
- Cellular functions of the protein kinase ATM and their relevance to human disease.Nature reviews. Molecular cell biology · 2021Review
- A novel, ataxic mouse model of ataxia telangiectasia caused by a clinically relevant nonsense mutation.eLife · 2021Article
- Article
- Ataxia Telangiectasia Mutated Protein Kinase: A Potential Master Puppeteer of Oxidative Stress-Induced Metabolic Recycling.Oxidative medicine and cellular longevity · 2021Review
- Mitochondria at the crossroads of ATM-mediated stress signaling and regulation of reactive oxygen species.Redox biology · 2020Review
- Redox Mechanisms in Neurodegeneration: From Disease Outcomes to Therapeutic Opportunities.Antioxidants & redox signaling · 2019Review
- Histone H2AX promotes neuronal health by controlling mitochondrial homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Anti-Oxidant Drugs: Novelties and Clinical Implications in Cerebellar Ataxias.Current neuropharmacology · 2019Review
- Antioxidant Defense, Redox Homeostasis, and Oxidative Damage in Children With Ataxia Telangiectasia and Nijmegen Breakage Syndrome.Frontiers in immunology · 2019Article
- Spontaneous DNA damage to the nuclear genome promotes senescence, redox imbalance and aging.Redox biology · 2018Article
- Nuclear membrane-localised NOX4D generates pro-survival ROS in FLT3-ITD-expressing AML.Oncotarget · 2017Article
- Oxidative stress, mitochondrial abnormalities and antioxidant defense in Ataxia-telangiectasia, Bloom syndrome and Nijmegen breakage syndrome.Redox biology · 2017Review
- Comparison of Selected Parameters of Redox Homeostasis in Patients with Ataxia-Telangiectasia and Nijmegen Breakage Syndrome.Oxidative medicine and cellular longevity · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Ataxia telangiectasia (A-T), a rare autosomal recessive disorder characterized by progressive cerebellar degeneration and a greatly increased incidence of cancer among other symptoms, is caused by a defective or missing ataxia telangiectasia mutated (ATM) gene. The ATM protein has roles in DNA repair and in the regulation of reactive oxygen species (ROS). Here, we provide, to our knowledge, the first evidence that NADPH oxidase 4 (NOX4) is involved in manifesting A-T disease. We showed that NOX4 expression levels are higher in A-T cells, and that ATM inhibition leads to increased NOX4 expression in normal cells. A-T cells exhibit elevated levels of oxidative DNA damage, DNA double-strand breaks and replicative senescence, all of which are partially abrogated by down-regulation of NOX4 with siRNA. Sections of degenerating cerebelli from A-T patients revealed elevated NOX4 levels. ATM-null mice exhibit A-T disease but they die from cancer before the neurological symptoms are manifested. Injecting Atm-null mice with fulvene-5, a specific inhibitor of NOX4 and NADPH oxidase 2 (NOX2), decreased their elevated cancer incidence to that of the controls. We conclude that, in A-T disease in humans and mice, NOX4 may be critical mediator and targeting it will open up new avenues for therapeutic intervention in neurodegeneration.
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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.