Journal
NATURE NEUROSCIENCE
Volume 13, Issue 11, Pages 1396-U133Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2660
Keywords
-
Categories
Funding
- ALS Therapy Alliance-CVS Pharmacy
- Marine Biological Laboratory
- ALS Association
- US National Institutes of Health
- National Institute on Neurological Disorders and Stroke [RO1NS067206-01, U01NS05225-03, R01NS050557-05, 1RC1NS068391-01, 1RC2NS070342-01]
- Canadian Institutes of Health Research
- Angel Fund
- ALS
Ask authors/readers for more resources
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 wildtype 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available