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Two hypotheses have dominated recent discussion of the toxicity of ALS mutant CuZnSOD proteins: the oligomerization hypothesis and the oxidative damage hypothesis. The oligomerization hypothesis maintains that mutant CuZnSOD proteins are, or become, misfolded and consequently oligomerize into increasingly high-molecular-weight species that ultimately lead to the death of motor neurons. The oxidative damage hypothesis maintains that ALS mutant CuZnSOD proteins catalyze oxidative reactions that damage substrates critical for viability of the affected cells. This perspective reviews some of the properties of both wild-type and mutant CuZnSOD proteins, suggests how these properties may be relevant to these two hypotheses, and proposes that these two hypotheses are not necessarily mutually exclusive.<\/jats:p>","DOI":"10.1073\/pnas.0730423100","type":"journal-article","created":{"date-parts":[[2003,4,1]],"date-time":"2003-04-01T14:25:08Z","timestamp":1049207108000},"page":"3617-3622","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":495,"title":["Misfolded CuZnSOD and amyotrophic lateral sclerosis"],"prefix":"10.1073","volume":"100","author":[{"given":"Joan Selverstone","family":"Valentine","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90025-1569; and Department of Biochemistry and the X-ray Crystallographic Core Laboratory, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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