Change search
ReferencesLink to record
Permanent link

Direct link
Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model mice
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. (Thomas Brännström)
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Show others and affiliations
2010 (English)In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 114, no 2, 408-418 p.Article in journal (Refereed) Published
Abstract [en]

Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from four different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intra-subunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, four were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.

Place, publisher, year, edition, pages
2010. Vol. 114, no 2, 408-418 p.
Keyword [en]
amyotrophic lateral sclerosis;endoplasmic reticulum;inclusion;proteomics;superoxide dismutase-1;transgenic mice
National Category
Medical and Health Sciences
Research subject
URN: urn:nbn:se:umu:diva-42155DOI: 10.1111/j.1471-4159.2010.06753.xISI: 000279077900007PubMedID: 20412382OAI: diva2:408773
Available from: 2011-04-06 Created: 2011-04-06 Last updated: 2013-10-31Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Bergemalm, DanielForsberg, KarinGraffmo, Karin SAndersen, Peter MBrännström, ThomasMarklund, Stefan L
By organisation
Clinical chemistryPathologyNeurology
In the same journal
Journal of Neurochemistry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 43 hits
ReferencesLink to record
Permanent link

Direct link