Dataset Information


Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.

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.


PROVIDER: S-EPMC2967729 | BioStudies | 2010-01-01

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4052529 | BioStudies
2012-01-01 | S-EPMC3325721 | BioStudies
2007-01-01 | S-EPMC1941502 | BioStudies
1000-01-01 | S-EPMC4035506 | BioStudies
2011-01-01 | S-EPMC3170425 | BioStudies
2010-01-01 | S-EPMC4376270 | BioStudies
2016-01-01 | S-EPMC5107152 | BioStudies
2017-01-01 | S-EPMC5349524 | BioStudies
2012-01-01 | S-EPMC3320864 | BioStudies
2014-01-01 | S-EPMC3951532 | BioStudies