ArticleHuman molecular genetics2014
Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia.
Article in Human molecular genetics, 2014. 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, 31 citations in OpenAlex.
- Macrophage migration inhibitory factor mediates joint capsule fibrosis via facilitating phospholipid metabolite PGE2 production in fibroblasts.Cellular and molecular life sciences : CMLS · 2025Article
- Altered Ca2+ responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes.Journal of cell science · 2025Article
- Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism.Life science alliance · 2024Article
- Blood RNA transcripts reveal similar and differential alterations in fundamental cellular processes in Alzheimer's disease and other neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- A new FRDA mouse model [Frontiers in neuroscience · 2023Article
- Metabolomics analysis reveals dysregulation in one carbon metabolism in Friedreich Ataxia.Molecular genetics and metabolism · 2022Article
- Neuroinflammation in Friedreich's Ataxia.International journal of molecular sciences · 2022Review
- Central Nervous System Therapeutic Targets in Friedreich Ataxia.Human gene therapy · 2020Review
- MUTYH: Not just polyposis.World journal of clinical oncology · 2020Review
- Mitochondria-Derived Damage-Associated Molecular Patterns in Neurodegeneration.Frontiers in immunology · 2017Review
- Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Human Frataxin Folds Via an Intermediate State. Role of the C-Terminal Region.Scientific reports · 2016Article
- Frataxin Deficiency Promotes Excess Microglial DNA Damage and Inflammation that Is Rescued by PJ34.PloS one · 2016Article
- Oxidative stress in inherited mitochondrial diseases.Free radical biology & medicine · 2015Review
- Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism.Journal of inherited metabolic disease · 2015Review
- Induction of COX-2-PGE2 synthesis by activation of the MAPK/ERK pathway contributes to neuronal death triggered by TDP-43-depleted microglia.Cell death & disease · 2015Article
- A novel GAA-repeat-expansion-based mouse model of Friedreich's ataxia.Disease models & mechanisms · 2015Article
- Spinocerebellar ataxia in the Italian Spinone dog is associated with an intronic GAA repeat expansion in ITPR1.Mammalian genome : official journal of the International Mammalian Genome Society · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
An inherited deficiency of the mitochondrial protein frataxin causes Friedreich's ataxia (FRDA); the mechanism by which this deficiency triggers neuro- and cardio-degeneration is unclear. Microarrays of neural tissue of animal models of the disease showed decreases in antioxidant genes, and increases in inflammatory genes. Cyclooxygenase (COX)-derived oxylipins are important mediators of inflammation. We measured oxylipin levels using tandem mass spectrometry and ELISAs in multiple cell and animal models of FRDA. Mass spectrometry revealed increases in concentrations of prostaglandins, thromboxane B2, 15-HETE and 11-HETE in cerebellar samples of knockin knockout mice. One possible explanation for the elevated oxylipins is that frataxin deficiency results in increased COX activity. While constitutive COX1 was unchanged, inducible COX2 expression was elevated over 1.35-fold (P < 0.05) in two Friedreich's mouse models and Friedreich's lymphocytes. Consistent with higher COX2 expression, its activity was also increased by 58% over controls. COX2 expression is driven by multiple transcription factors, including activator protein 1 and cAMP response element-binding protein, both of which were elevated over 1.52-fold in cerebella. Taken together, the results support the hypothesis that reduced expression of frataxin leads to elevation of COX2-mediated oxylipin synthesis stimulated by increases in transcription factors that respond to increased reactive oxygen species. These findings support a neuroinflammatory mechanism in FRDA, which has both pathomechanistic and therapeutic implications.
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