Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Gurney ME et al. Benefit of vitamin E, Riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. 1999 references Aguirre et al. Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress.
Most evidence now is that the mutation results in a gain of function.
In the Aguirre paper, evidence is presented that ALS fibroblasts are more sensitive to various types of oxidative stress, and particularly to the NO generating agent SIN-1. In the Corson paper, evidence is presented suggesting that there are multiple pathways for oxidative stress related to abnormal exposure of the copper atom within the SOD-1 molecule. Experimental ideas related to both papers were discussed also. This enzyme, which has little impact on mouse knockouts, may mediate considerable amounts of cell damage following ischemia. Because the enzyme does not appear essential over the short term, it seems quite logical that inhibitors might be given shortly after a stroke to reduce the size of the injury.