Sökning: onr:"swepub:oai:DiVA.org:umu-191464" >
SOD1 mutations asso...
SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity
-
- Berdynski, Mariusz (författare)
- Umeå universitet,Neurovetenskaper,Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
-
- Miszta, Przemysław (författare)
- Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland
-
- Safranow, Krzysztof (författare)
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. Str., Szczecin, Poland
-
visa fler...
-
- Andersen, Peter M., 1962- (författare)
- Umeå universitet,Neurovetenskaper
-
- Morita, Mitsuya (författare)
- Division of Neurology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan
-
- Filipek, Sławomir (författare)
- Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland
-
- Żekanowski, Cezary (författare)
- Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
-
- Kuźma-Kozakiewicz, Magdalena (författare)
- Department of Neurology, Medical University of Warsaw, Warsaw, Poland; Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland
-
visa färre...
-
(creator_code:org_t)
- 2022-01-07
- 2022
- Engelska.
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://umu.diva-por... (primary) (Raw object)
-
https://www.nature.c...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Mutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons. The clinical phenotype of ALS shows inter- and intrafamilial heterogeneity. The aim of the study was to analyze the relations between individual SOD1 mutations and the clinical presentation using in silico methods to assess the SOD1 mutations severity. We identified SOD1 causative variants in a group of 915 prospectively tested consecutive Polish ALS patients from a neuromuscular clinical center, performed molecular modeling of mutated SOD1 proteins and in silico analysis of mutation impact on clinical phenotype and survival analysis of associations between mutations and hazard of clinical end-points. Fifteen SOD1 mutations were identified in 21.1% familial and 2.3% sporadic ALS cases. Their effects on SOD1 protein structure and functioning inferred from molecular modeling and in silico analyses correlate well with the clinical data. Molecular modeling results support the hypothesis that folding intermediates rather than mature SOD1 protein give rise to the source of cytotoxic conformations in ALS. Significant associations between type of mutation and clinical end-points were found.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas