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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Active Transport, Cell Nucleus, Antioxidants, Disease Progression, Fibroblasts, Friedreich Ataxia, Gene Expression Regulation, Humans, Hydrogen Peroxide, Iron-Sulfur Proteins, Models, Biological, NF-E2-Related Factor 2, Neurons, Oxidation-Reduction, Oxidative Stress, Signal Transduction.
user
Does impaired nuclear Nrf2 translocation undermine the oxidative stress response in Friedreich ataxia? Context: Friedreich ataxia originates from a decrease in mitochondrial frataxin, which causes the death of a subset of neurons. The biochemical hallmarks of the disease include low activity of the iron sulfur cluster-containing proteins (ISP) and impairment of antioxidant defense mechanisms that may play a major role in disease progression. We thus investigated signaling pathways involved in antioxidant defense mechanisms. We showed that cultured fibroblasts from patients with Friedreich ataxia exhibited hypersensitivity to oxidative insults because of an impairment in the Nrf2 signaling pathway, which led to faulty induction of antioxidant enzymes. This impairment originated from previously reported actin remodeling by hydrogen peroxide.
assistant
Thus, the defective machinery for ISP synthesis by causing mitochondrial iron dysmetabolism increases hydrogen peroxide production that accounts for the increased susceptibility to oxidative stress. Final Decision: yes