| First Author | Ferrante RJ | Year | 1997 |
| Journal | Ann Neurol | Volume | 42 |
| Issue | 3 | Pages | 326-34 |
| PubMed ID | 9307254 | Mgi Jnum | J:43347 |
| Mgi Id | MGI:1097527 | Doi | 10.1002/ana.410420309 |
| Citation | Ferrante RJ, et al. (1997) Increased 3-nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation. Ann Neurol 42(3):326-34 |
| abstractText | Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS), Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of function may be an enhanced ability of the mutant SOD1 to generate OI-I radicals or to facilitate peroxynitrite-mediated nitration of proteins, We found significant increases in concentrations of 3-nitrotyrosine, a marker of peroxyitrite-mediated nitration, in upper and lower spinal cord and in cerebra cortex of transgenic mice with the FALS-associated G93A mutation, Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3- Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde- modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration. |
