ArticleStem cell reports2022
Iron accumulation induces oxidative stress, while depressing inflammatory polarization in human iPSC-derived microglia.
Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Microglial 5-LOX-activating protein antagonism alleviates leukotriene-driven neuroinflammation.Acta neuropathologica · 2026Article
- Ferritin in ferroptosis: Implications for neurodegenerative diseases (Review).International journal of molecular medicine · 2026Review
- The iron-energy metabolism axis in Alzheimer's pathogenesis: from mechanisms to interventions.Cell death discovery · 2026Review
- Mutational scanning reveals oncogenic CTNNB1 mutations have diverse effects on signaling.Nature genetics · 2026Article
- Ferroptosis in microglial activation: a systematic review and multidata comparison.Brain communications · 2026Review
- 27-Hydroxycholesterol triggers microglial senescence subsequent to iron over-loading contributes to brain aging, suppressed by Deferoxamine.npj aging · 2025Article
- Microglia from patients with multiple sclerosis display a cell-autonomous immune activation state.Journal of neuroinflammation · 2025Article
- Spatial proteomics of Alzheimer's disease-specific human microglial states.Nature immunology · 2025Article
- Modeling neuroinflammatory interactions between microglia and astrocytes in a human iPSC-based coculture platform.Cell communication and signaling : CCS · 2025Article
- Inflammation alters myeloid cell and oligodendroglial iron-handling in multiple sclerosis.Acta neuropathologica communications · 2025Article
- Exploring Iron Deposition Patterns Using Light and Electron Microscopy in the Mouse Brain Across Aging and Alzheimer's Disease Pathology Conditions.Journal of neurochemistry · 2025Article
- Spatial mapping of the AA-PGEActa neuropathologica · 2025Article
- Inhibition of iron-induced cofilin activation and inflammation in microglia by a novel cofilin inhibitor.Journal of neurochemistry · 2025Article
- Iron induces blood-brain barrier alteration contributing to cognitive impairment in β-thalassaemia mice.Scientific reports · 2025Article
- Modulation of glucocorticoid receptor function under iron overload.Frontiers in immunology · 2025Article
- Role of NRF2 in Pathogenesis of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Inhibition of SLC40A1 represses osteoblast formation via inducing iron accumulation and activating the PERK/ATF4/CHOP pathway mediated oxidative stress.Redox report : communications in free radical research · 2024Article
- Fenebrutinib, a Bruton's tyrosine kinase inhibitor, blocks distinct human microglial signaling pathways.Journal of neuroinflammation · 2024Article
- Knockdown of microglial iron import gene, Slc11a2, worsens cognitive function and alters microglial transcriptional landscape in a sex-specific manner in the APP/PS1 model of Alzheimer's disease.Journal of neuroinflammation · 2024Article
- Deterioration of neuroimmune homeostasis in Alzheimer's Disease patients who survive a COVID-19 infection.Journal of neuroinflammation · 2024Article
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron accumulation in microglia has been observed in Alzheimer's disease and other neurodegenerative disorders and is thought to contribute to disease progression through various mechanisms, including neuroinflammation. To study this interaction, we treated human induced pluripotent stem cell-derived microglia (iPSC-MG) with iron, in combination with inflammatory stimuli such as interferon gamma (IFN-γ) and amyloid β. Both IFN-γ and iron treatment increased labile iron levels, but only iron treatment led to a consistent increase of ferritin levels, reflecting long-term iron storage. Therefore, in iPSC-MG, ferritin appeared to be regulated by iron revels rather than inflammation. Further investigation showed that while IFN-γ induced pro-inflammatory activation, iron treatment dampened both classic pro- and anti-inflammatory activation on a transcriptomic level. Notably, iron-loaded microglia showed strong upregulation of cellular stress response pathways, the NRF2 pathway, and other oxidative stress pathways. Functionally, iPSC-MG exhibited altered phagocytosis and impaired mitochondrial metabolism following iron treatment. Collectively, these data suggest that in MG, in contrast to current hypotheses, iron treatment does not result in pro-inflammatory activation, but rather dampens it and induces oxidative stress.
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