Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 34, Issue 11, Pages 1383-1389Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0891-5849(03)00153-9
Keywords
superoxide dismutase; amyotrophic lateral sclerosis; superoxide reductase; superoxide; free radicals
Funding
- NIDDK NIH HHS [R01 DK 59868] Funding Source: Medline
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FALS-associated missense mutations of SOD1 exhibit a toxic gain of function that leads to the death of motor neurons. The explanations for this toxicity fall into two broad categories. One involves a gain of some oxidative activity, while the second involves a gain of protein: protein interactions. Among the postulated oxidative activities are the following: (i) peroxidase action; (ii) superoxide reductase action; and, (iii) the enhancement of production of O-2(-) by partial reversal of the normal SOD activity, which then leads to increased formation of ONOO-. We will herein concentrate on evaluating the relative merits of these oxidative hypotheses and consider whether the experiments with transgenic animals that purport to disprove these oxidative explanations really do so. (C) 2003 Elsevier Inc.
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