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The motor system is...
The motor system is exceptionally vulnerable to absence of the ubiquitously expressed superoxide dismutase-1
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- Park, Julien H. (author)
- Umeå universitet,Neurovetenskaper,Department of General Paediatrics, University of Münster, Münster, Germany
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- Nordström, Ulrika (author)
- Umeå universitet,Neurovetenskaper
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- Tsiakas, Konstantinos (author)
- Department of Paediatrics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
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- Keskin, Isil, 1987- (author)
- Umeå universitet,Patologi
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- Elpers, Christiane (author)
- Department of General Paediatrics, University of Münster, Münster, Germany
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- Mannil, Manoj (author)
- Clinic for Radiology, University Hospital Münster, WWU University of Münster, Münster, Germany
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- Heller, Raoul (author)
- Starship Children's Health, Auckland City Hospital, Auckland, New Zealand
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- Nolan, Melinda (author)
- Starship Children's Health, Auckland City Hospital, Auckland, New Zealand
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- Alburaiky, Salam (author)
- Starship Children's Health, Auckland City Hospital, Auckland, New Zealand
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- Zetterström, Per (author)
- Umeå universitet,Klinisk kemi
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- Hempel, Maja (author)
- Department of Paediatrics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany
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- Schara-Schmidt, Ulrike (author)
- Department of Paediatric Neurology, University Hospital Essen, Essen, Germany
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- Biskup, Saskia (author)
- CeGAT GmbH and Praxis für Humangenetik Tübingen, Tübingen, Germany
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- Steinacker, Petra (author)
- Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
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- Otto, Markus (author)
- Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
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- Weishaupt, Jochen (author)
- Division for Neurodegenerative Diseases, Department of Neurology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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- Hahn, Andreas (author)
- Department of Child Neurology, Justus Liebig University, Giessen, Germany
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- Santer, Rene (author)
- Department of Paediatrics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
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- Marquardt, Thorsten (author)
- Department of General Paediatrics, University of Münster, Münster, Germany
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- Marklund, Stefan L. (author)
- Umeå universitet,Klinisk kemi
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- Andersen, Peter M., 1962- (author)
- Umeå universitet,Neurovetenskaper
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(creator_code:org_t)
- 2023-01-27
- 2023
- English.
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In: Brain Communications. - : Oxford University Press. - 2632-1297. ; 5:1
- Related links:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
Close
- Superoxide dismutase-1 is a ubiquitously expressed antioxidant enzyme. Mutations in SOD1 can cause amyotrophic lateral sclerosis, probably via a toxic gain-of-function involving protein aggregation and prion-like mechanisms. Recently, homozygosity for loss-of-function mutations in SOD1 has been reported in patients presenting with infantile-onset motor neuron disease. We explored the bodily effects of superoxide dismutase-1 enzymatic deficiency in eight children homozygous for the p.C112Wfs∗11 truncating mutation. In addition to physical and imaging examinations, we collected blood, urine and skin fibroblast samples. We used a comprehensive panel of clinically established analyses to assess organ function and analysed oxidative stress markers, antioxidant compounds, and the characteristics of the mutant Superoxide dismutase-1. From around 8 months of age, all patients exhibited progressive signs of both upper and lower motor neuron dysfunction, cerebellar, brain stem, and frontal lobe atrophy and elevated plasma neurofilament concentration indicating ongoing axonal damage. The disease progression seemed to slow down over the following years. The p.C112Wfs∗11 gene product is unstable, rapidly degraded and no aggregates were found in fibroblast. Most laboratory tests indicated normal organ integrity and only a few modest deviations were found. The patients displayed anaemia with shortened survival of erythrocytes containing decreased levels of reduced glutathione. A variety of other antioxidants and oxidant damage markers were within normal range. In conclusion, non-neuronal organs in humans show a remarkable tolerance to absence of Superoxide dismutase-1 enzymatic activity. The study highlights the enigmatic specific vulnerability of the motor system to both gain-of-function mutations in SOD1 and loss of the enzyme as in the here depicted infantile superoxide dismutase-1 deficiency syndrome.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- ALS
- infantile motor neuron disease
- oxygen toxicity
- SOD1
- spasticity
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Park, Julien H.
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Nordström, Ulrik ...
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Tsiakas, Konstan ...
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Keskin, Isil, 19 ...
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Elpers, Christia ...
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Mannil, Manoj
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Heller, Raoul
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Nolan, Melinda
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Alburaiky, Salam
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Zetterström, Per
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Hempel, Maja
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Schara-Schmidt, ...
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Biskup, Saskia
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Steinacker, Petr ...
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Otto, Markus
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Weishaupt, Joche ...
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Hahn, Andreas
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Santer, Rene
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Marquardt, Thors ...
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Marklund, Stefan ...
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Andersen, Peter ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Brain Communicat ...
- By the university
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Umeå University