ArticleNeurotoxicity research2022
The Gpx4NIKO Mouse Is a Versatile Model for Testing Interventions Targeting Ferroptotic Cell Death of Spinal Motor Neurons.
Article in Neurotoxicity research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Ferroptosis Resistance: Redundant Antioxidant Networks Are a Barrier to Cancer Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Article
- Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.Bone research · 2025Review
- Beyond oxidative stress: Ferroptosis as a novel orchestrator in neurodegenerative disorders.Frontiers in immunology · 2025Review
- The Role of Ferroptosis in Amyotrophic Lateral Sclerosis Treatment.Neurochemical research · 2024Review
- Ferroptosis: A double-edged sword.Cell death discovery · 2024Review
- Mechanisms of Ferritinophagy and Ferroptosis in Diseases.Molecular neurobiology · 2024Review
- Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.Frontiers in cellular neuroscience · 2024Review
- What Is the Role of Ferroptosis in Neurodegeneration?Neurology · 2023Article
- Substance abuse and neurodegenerative diseases: focus on ferroptosis.Archives of toxicology · 2023Review
- Mitochondrial Peroxiredoxin 3 Is Rapidly Oxidized and Hyperoxidized by Fatty Acid Hydroperoxides.Antioxidants (Basel, Switzerland) · 2023Article
- The emerging roles of ferroptosis in cells of the central nervous system.Frontiers in neuroscience · 2022Review
- The Classification and Prediction of Ferroptosis-Related Genes in ALS: A Pilot Study.Frontiers in genetics · 2022Article
- Mechanisms of Ferroptosis and Emerging Links to the Pathology of Neurodegenerative Diseases.Frontiers in aging neuroscience · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The degeneration and death of motor neurons lead to motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Although the exact mechanism by which motor neuron degeneration occurs is not well understood, emerging evidence implicates the involvement of ferroptosis, an iron-dependent oxidative mode of cell death. We reported previously that treating Gpx4NIKO mice with tamoxifen to ablate the ferroptosis regulator glutathione peroxidase 4 (GPX4) in neurons produces a severe paralytic model resembling an accelerated form of ALS that appears to be caused by ferroptotic cell death of spinal motor neurons. In this study, in support of the role of ferroptosis in this model, we found that the paralytic symptoms and spinal motor neuron death of Gpx4NIKO mice were attenuated by a chemical inhibitor of ferroptosis. In addition, we observed that the paralytic symptoms of Gpx4NIKO mice were malleable and could be tapered by lowering the dose of tamoxifen, allowing for the generation of a mild paralytic model without a rapid onset of death. We further used both models to evaluate mitochondrial reactive oxygen species (mtROS) in the ferroptosis of spinal motor neurons and showed that overexpression of peroxiredoxin 3, a mitochondrial antioxidant defense enzyme, ameliorated symptoms of the mild but not the severe model of the Gpx4NIKO mice. Our results thus indicate that the Gpx4NIKO mouse is a versatile model for testing interventions that target ferroptotic death of spinal motor neurons in vivo.
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