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How\u2014or indeed whether\u2014protein aggregation\n and inclusion body formation cause neurotoxicity are presently unknown.\n Here, we show that the capacity of superoxide dismutase (SOD) to\n aggregate into biochemically distinct, high molecular weight, insoluble\n protein complexes (IPCs) is a gain of function associated with\n mutations linked to autosomal dominant familial amyotrophic lateral\n sclerosis. SOD IPCs are detectable in spinal cord extracts from\n transgenic mice expressing mutant SOD several months before inclusion\n bodies and motor neuron pathology are apparent. Sequestration of mutant\n SOD into cytoplasmic inclusion bodies resembling aggresomes requires\n retrograde transport on microtubules. These data indicate that\n aggregation and inclusion body formation are mechanistically and\n temporally distinct processes.<\/jats:p>","DOI":"10.1073\/pnas.220417997","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"12571-12576","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":501,"title":["Formation of high molecular weight complexes of mutant Cu,Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis"],"prefix":"10.1073","volume":"97","author":[{"given":"Jennifer A.","family":"Johnston","sequence":"first","affiliation":[{"name":"Department of Biological Sciences and Program in\r Neurosciences, Stanford University, Stanford, CA 94305-5020"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muffie J.","family":"Dalton","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and 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