ArticlePloS one2021
Iron activates microglia and directly stimulates indoleamine-2,3-dioxygenase activity in the N171-82Q mouse model of Huntington's disease.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- Role of iron in brain development, aging, and neurodegenerative diseases.Annals of medicine · 2025Review
- Targeting IDO1 in Huntington's Disease: Network Pharmacology and Preclinical Evidence from Coffea arabica.Neurochemical research · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Inhibition of iron-induced cofilin activation and inflammation in microglia by a novel cofilin inhibitor.Journal of neurochemistry · 2025Article
- Ferroptosis in central nervous system injuries: molecular mechanisms, diagnostic approaches, and therapeutic strategies.Frontiers in cellular neuroscience · 2025Review
- Ferroptosis in radiation-induced brain injury: roles and clinical implications.Biomedical engineering online · 2024Review
- Heavy Metal Interactions with Neuroglia and Gut Microbiota: Implications for Huntington's Disease.Cells · 2024Review
- Brain Iron Dyshomeostasis and Ferroptosis in Alzheimer's Disease Pathophysiology: Two Faces of the Same Coin.Aging and disease · 2024Review
- Widespread selenium deficiency in the brain of cases with Huntington's disease presents a new potential therapeutic target.EBioMedicine · 2023Article
- Review
- Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study.AJNR. American journal of neuroradiology · 2023Article
- Insight into the potential role of ferroptosis in neurodegenerative diseases.Frontiers in cellular neuroscience · 2022Review
- The association between cerebrospinal ferritin and soluble triggering receptor expressed on myeloid cells 2 along Alzheimer's continuum.Frontiers in neurology · 2022Article
- Species Differences in Tryptophan Metabolism and Disposition.International journal of tryptophan research : IJTR · 2022Review
- Iron Dyshomeostasis and Ferroptosis: A New Alzheimer's Disease Hypothesis?Frontiers in aging neuroscience · 2022Review
- NADFrontiers in molecular biosciences · 2021Review
- Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Huntington's disease (HD) is a neurodegenerative disorder caused by a dominant CAG-repeat expansion in the huntingtin gene. Microglial activation is a key feature of HD pathology, and is present before clinical disease onset. The kynurenine pathway (KP) of tryptophan degradation is activated in HD, and is thought to contribute to disease progression. Indoleamine-2,3-dioxygenase (IDO) catalyzes the first step in this pathway; this and other pathway enzymes reside with microglia. While HD brain microglia accumulate iron, the role of iron in promoting microglial activation and KP activity is unclear. Here we utilized the neonatal iron supplementation model to investigate the relationship between iron, microglial activation and neurodegeneration in adult HD mice. We show in the N171-82Q mouse model of HD microglial morphologic changes consistent with immune activation. Neonatal iron supplementation in these mice promoted neurodegeneration and resulted in additional microglial activation in adults as determined by increased soma volume and decreased process length. We further demonstrate that iron activates IDO, both in brain lysates and purified recombinant protein (EC50 = 1.24 nM). Brain IDO activity is increased by HD. Neonatal iron supplementation further promoted IDO activity in cerebral cortex, altered KP metabolite profiles, and promoted HD neurodegeneration as measured by brain weights and striatal volumes. Our results demonstrate that dietary iron is an important activator of microglia and the KP pathway in this HD model, and that this occurs in part through a direct effect on IDO. The findings are relevant to understanding how iron promotes neurodegeneration in HD.
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