CuZn-superoxide dismutase in D90A heterozygotes from recessive and dominant ALS pedigrees

P. Andreas Jonsson, Åsa Bäckstrand, Peter M. Andersen, Johan Jacobsson, Matthew Parton, Chris Shaw, Robert Swingler, Pamela J. Shaw, Wim Robberecht, Albert C. Ludolph, Teepu Siddique, Veronica I. Skvortsova, Stefan L. Marklund

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Mutations in CuZn-superoxide dismutase (CuZn-SOD) have been linked to ALS. In most cases ALS is inherited as a dominant trait and there is marked reduction in CuZn-SOD activity in samples from the patients. The D90A mutation, however, mostly causes ALS as a recessive trait and shows near normal CuZn-SOD activity. A few familial and sporadic ALS cases heterozygous for the D90A mutation have also been found. Haplotype analysis of both types of D90A families has suggested that all recessive cases share a common founder and may carry a protective factor located close to the D90A mutant CuZn-SOD locus. To search for effects of a putative protective factor we analysed erythrocytes from D90A heterozygous individuals for SOD activity by a direct assay, subunit composition by immunoblotting, and zymogram pattern formed by isoelectric focusing and SOD staining. Included were heterozygotes from 17 recessive families, and from 2 dominant families and 4 apparently sporadic cases. The CuZn-SOD activity in the recessive and dominant groups was found to be equal, and 95% of controls. The ratio between mutant and wildtype subunits was likewise equal and 0.8:1 in both groups. The zymograms revealed multiple bands representing homo- and heterodimers. There were, however, no differences between the groups in patterns or in ratios between the molecular forms. In conclusion we find no evidence from analyses in erythrocytes that the putative protective factor in recessive families acts by simple downregulating the synthesis or altering the molecular structure or turnover of the mutant enzyme.

Original languageEnglish (US)
Pages (from-to)327-333
Number of pages7
JournalNeurobiology of Disease
Volume10
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Amyotrophic lateral sclerosis
  • Erythrocytes
  • Oxygen radicals
  • Superoxide dismutase

ASJC Scopus subject areas

  • Neurology

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    Jonsson, P. A., Bäckstrand, Å., Andersen, P. M., Jacobsson, J., Parton, M., Shaw, C., Swingler, R., Shaw, P. J., Robberecht, W., Ludolph, A. C., Siddique, T., Skvortsova, V. I., & Marklund, S. L. (2002). CuZn-superoxide dismutase in D90A heterozygotes from recessive and dominant ALS pedigrees. Neurobiology of Disease, 10(3), 327-333. https://doi.org/10.1006/nbdi.2002.0508