Mutant Cu/Zn Superoxide Dismutase (A4V) Turnover Is Altered in Cells Containing Inclusions.
| Autor: | Farrawell NE; Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia.; School of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia., Yerbury JJ; Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia.; School of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Frontiers in molecular neuroscience [Front Mol Neurosci] 2021 Nov 03; Vol. 14, pp. 771911. Date of Electronic Publication: 2021 Nov 03 (Print Publication: 2021). |
| DOI: | 10.3389/fnmol.2021.771911 |
| Abstrakt: | SOD1 mutations account for ∼20% of familial amyotrophic lateral sclerosis (ALS) cases in which the hallmark pathological feature is insoluble SOD1 aggregates within motor neurons. Here, we investigated the degradation and synthesis of mutant SOD1 to determine whether the aggregation of mutant SOD1 A4V affects these processes. We confirm that, in general, the degradation of mutant SOD1 A4V occurs at a significantly faster rate than wild-type SOD1. We also report that the turnover and synthesis of mutant SOD1 A4V is impaired in the presence of insoluble SOD1 A4V aggregates. However, the timing of aggregation of SOD1 A4V did not coincide with UPS dysfunction. Together, these results reveal the impact of SOD1 aggregation on protein degradation pathways, highlighting the importance of the UPS in preventing neurodegenerative disorders such as ALS. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Farrawell and Yerbury.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|