Title |
Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration
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Published in |
Brain, December 2015
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DOI | 10.1093/brain/awv350 |
Pubmed ID | |
Authors |
Eliska Holzerova, Katharina Danhauser, Tobias B Haack, Laura S Kremer, Marlen Melcher, Irina Ingold, Sho Kobayashi, Caterina Terrile, Petra Wolf, Jörg Schaper, Ertan Mayatepek, Fabian Baertling, José Pedro Friedmann Angeli, Marcus Conrad, Tim M Strom, Thomas Meitinger, Holger Prokisch, Felix Distelmaier |
Abstract |
Thioredoxin 2 (TXN2; also known as Trx2) is a small mitochondrial redox protein essential for the control of mitochondrial reactive oxygen species homeostasis, apoptosis regulation and cell viability. Exome sequencing in a 16-year-old adolescent suffering from an infantile-onset neurodegenerative disorder with severe cerebellar atrophy, epilepsy, dystonia, optic atrophy, and peripheral neuropathy, uncovered a homozygous stop mutation in TXN2. Analysis of patient-derived fibroblasts demonstrated absence of TXN2 protein, increased reactive oxygen species levels, impaired oxidative stress defence and oxidative phosphorylation dysfunction. Reconstitution of TXN2 expression restored all these parameters, indicating the causal role of TXN2 mutation in disease development. Supplementation with antioxidants effectively suppressed cellular reactive oxygen species production, improved cell viability and mitigated clinical symptoms during short-term follow-up. In conclusion, our report on a patient with TXN2 deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and energy metabolism. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 4 | 40% |
United States | 2 | 20% |
Unknown | 4 | 40% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 6 | 60% |
Science communicators (journalists, bloggers, editors) | 4 | 40% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Canada | 1 | 1% |
Unknown | 75 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 21 | 28% |
Researcher | 10 | 13% |
Student > Bachelor | 7 | 9% |
Other | 7 | 9% |
Student > Master | 5 | 7% |
Other | 12 | 16% |
Unknown | 14 | 18% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 24 | 32% |
Medicine and Dentistry | 8 | 11% |
Agricultural and Biological Sciences | 6 | 8% |
Neuroscience | 4 | 5% |
Immunology and Microbiology | 3 | 4% |
Other | 13 | 17% |
Unknown | 18 | 24% |