ArticleJournal of neuroinflammation2019
Iron accentuated reactive oxygen species release by NADPH oxidase in activated microglia contributes to oxidative stress in vitro.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 122 citations in OpenAlex.
- Monomethyl Fumarate Modulates Iron Metabolism and Mitochondrial Function in Microglia with Implications for Multiple Sclerosis Progression.Cellular and molecular neurobiology · 2026Article
- ZFP36L1 Enhances Microglial Ferroptosis in Ischemic Stroke by Reducing FTO-Mediated N6-Methyladenosine Demethylation of ACSL1 mRNA.The Kaohsiung journal of medical sciences · 2026Article
- Article
- Splenic Macrophage Activation and Disordered Heme-Iron Metabolism in a Mouse Model of Acute Hepatic Encephalopathy.International journal of molecular sciences · 2026Article
- Autophagy-NLRP3 Inflammasome Crosstalk in Microglia: A Therapeutic Target for Multiple Sclerosis.Inflammation · 2026Review
- Astrocyte-specific deletion of ceruloplasmin exacerbates oxidative stress and demyelination in the spinal cord in a murine model of multiple sclerosis.Neurobiology of disease · 2026Article
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Reprogramming brain-resident macrophages: from disease drivers to therapeutic allies in neurological disorders.Frontiers in cellular neuroscience · 2026Review
- Beyond Radical Scavengers: Focus on NADPH Oxidases (NOX) Inhibitors as New Agents for Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Borax Triggers Ferroptosis by Modulating the TfR1/GPX4/ACSL4 Pathway in Prostate Cancer Cells with Differential Androgen Sensitivity.Biological trace element research · 2025Article
- RRBP1 Inhibition Reduces Microglial M1 Polarization and Inflammation-Mediated Neuronal Loss and Oxidative Stress by Regulating ERK Pathway in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Labile iron overload reprograms microglia and neurons for lipid droplet synthesis in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- Effects of iron accumulation and its chelation on oxidative stress in intracortical implants.Acta biomaterialia · 2025Article
- The Roles of DMT1 in Inflammatory and Degenerative Diseases.Molecular neurobiology · 2025Review
- Altered Gut Microbiota Contributes to Acute-Respiratory-Distress-Syndrome-Related Depression through Microglial Neuroinflammation.Research (Washington, D.C.) · 2025Article
- Sepsis-associated encephalopathy: Mechanisms, Diagnosis, and Treatments update.International journal of biological sciences · 2025Review
- Crosstalk between neuroinflammation and ferroptosis: Implications for Parkinson's disease progression.Frontiers in pharmacology · 2025Review
- Microglial Mechanisms and Therapeutic Potential in Brain Injury Post-Intracerebral Hemorrhage.Journal of inflammation research · 2025Review
- NOX2 in Alzheimer's and Parkinson's disease.Redox biology · 2024Review
- Unlocking ferroptosis in prostate cancer - the road to novel therapies and imaging markers.Nature reviews. Urology · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExcessive iron contributes to oxidative stress after central nervous system injury. NADPH oxidase (NOX) enzymes are upregulated in microglia after pro-inflammatory activation and contribute to oxidative stress. The relationship between iron, microglia, NOX, and oxidative stress is currently unclear.
methodsWe evaluated the effects of iron on lipopolysaccharide (LPS)-activated microglia and its secondary effect within neuronal co-cultures. Further, NOX2 and four specific inhibitors were tested to evaluate the relationship with the reactive oxygen species (ROS)-producing enzymes.
resultsAn iron dose-dependent increase in ROS production among microglia treated with LPS was identified. Interestingly, despite this increase in ROS, inflammatory polarization alterations were not detected among the microglia after exposure to iron and LPS. Co-culture experimentation between primary neurons and exposed microglia (iron and LPS) significantly reduced neuronal cell number at 24 h, suggesting a profound neurotoxic effect despite the lack of a change in polarization phenotype. NOX2 and NOX4 inhibition significantly reduced ROS production among microglia exposed to iron and LPS and reduced neuronal damage and death in response to microglial co-culture.
conclusionsIn conclusion, iron significantly increased ROS production and neurotoxicity without exacerbating LP-activated microglia phenotype in vitro, suggesting that iron contributes to microglia-related oxidative stress, and this may be a viable therapeutic target for injury or neurodegeneration. Further, this study highlights both NOX2 and NOX4 as potential therapeutic targets in the treatment of iron-induced microglia-related inflammation and neurotoxicity.
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