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Abstract
[...]an important implication of the connection between SOD1 and ALS is that the degeneration of motor neurons in ALS may be triggered by oxidative injury by free radicals.1 Subsequent reports that the SOD1 mutations in familial ALS reduce the activity of this enzyme2,3 supported the hypothesis that the neurotoxic free radical is the superoxide anion itself. An alternative hypothesis is that the mutations might impart a new, harmful property to the enzyme.4 This gain-of-function hypothesis is based primarily on the fact that familial ALS is dominantly inherited; only one copy of the abnormal gene is needed to cause the disease. Because most enzymes are present in excess, one normally functioning gene is usually enough for normal cellular function. [...]these transgenic mice with ALS are of enormous importance as a research tool.