| First Author | Taylor DM | Year | 2007 |
| Journal | J Biol Chem | Volume | 282 |
| Issue | 22 | Pages | 16329-35 |
| PubMed ID | 17389599 | Mgi Jnum | J:122717 |
| Mgi Id | MGI:3715133 | Doi | 10.1074/jbc.M610119200 |
| Citation | Taylor DM, et al. (2007) Tryptophan 32 potentiates aggregation and cytotoxicity of a copper/zinc superoxide dismutase mutant associated with familial amyotrophic lateral sclerosis. J Biol Chem 282(22):16329-35 |
| abstractText | One familial form of the neurodegenerative disease, amyotrophic lateral sclerosis, is caused by gain-of-function mutations in the gene encoding copper/zinc superoxide dismutase (SOD-1). This study provides in vivo evidence that normally occurring oxidative modification to SOD-1 promotes aggregation and toxicity of mutant proteins. The oxidation of Trp-32 was identified as a normal modification being present in both wild-type enzyme and SOD-1 with the disease-causing mutation, G93A, isolated from erythrocytes. Mutating Trp-32 to a residue with a slower rate of oxidative modification, phenylalanine, decreased both the cytotoxicity of mutant SOD-1 and its propensity to form cytoplasmic inclusions in motor neurons of dissociated mouse spinal cord cultures. |
