Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.
Publication/Presentation Date
11-1-2010
Abstract
Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS.
Volume
13
Issue
11
First Page
1396
Last Page
1403
ISSN
1546-1726
Published In/Presented At
Bosco, D. A., Morfini, G., Karabacak, N. M., Song, Y., Gros-Louis, F., Pasinelli, P., Goolsby, H., Fontaine, B. A., Lemay, N., McKenna-Yasek, D., Frosch, M. P., Agar, J. N., Julien, J. P., Brady, S. T., & Brown, R. H., Jr (2010). Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS. Nature neuroscience, 13(11), 1396–1403. https://doi.org/10.1038/nn.2660
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
20953194
Department(s)
Administration and Leadership
Document Type
Article