{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:47:52Z","timestamp":1771462072260,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T00:00:00Z","timestamp":1332201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:sec><jats:label\/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2012) <jats:bold>121<\/jats:bold>, 475\u2013485.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis. The Cu\u2010binding capacity of SOD1 has spawned hypotheses that implicate metal\u2010mediated production of reactive species as a potential mechanism of toxicity. In past experiments, we have tested such hypotheses by mutating residues in SOD1 that normally coordinate the binding of Cu, finding that such mutants retain the capacity to induce motor neuron disease. We now describe the lack of disease in mice that express a variant of human SOD1 in which residues that coordinate the binding of Cu and Zn have been mutated (SODMD). SODMD encodes three disease\u2010causing and four experimental mutations that ultimately eliminate all histidines involved in the binding of metals; and includes one disease\u2010causing and one experimental mutation that eliminate secondary metal binding at C6 and C111. We show that the combined effect of these mutations produces a protein that is unstable but does not aggregate on its own, is not toxic, and does not induce disease when co\u2010expressed with high levels of wild\u2010type SOD1. In cell culture models, we determine that the combined mutation of C6 and C111 to G and S, respectively, dramatically reduces the aggregation propensity of SODMD and may account for the lack of toxicity for this mutant.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07690.x","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T15:26:02Z","timestamp":1329233162000},"page":"475-485","source":"Crossref","is-referenced-by-count":23,"title":["A novel variant of human superoxide dismutase 1 harboring amyotrophic lateral sclerosis\u2010associated and experimental mutations in metal\u2010binding residues and free cysteines lacks toxicity <i>in vivo<\/i>"],"prefix":"10.1111","volume":"121","author":[{"given":"Mercedes","family":"Prudencio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman","family":"Lelie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilda H.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian P.","family":"Whitelegge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan S.","family":"Valentine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Borchelt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,3,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704307104"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.17.8292"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.7.3234"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1998.0178"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80272-X"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807058105"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705657200"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602046103"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn131"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb935"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2003.10.004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1016\/S0021-9258(19)44055-6","article-title":"On the stability of bovine superoxide dismutase The effects of metals.","volume":"248","author":"Forman H. 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