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We demonstrate by biochemical and morphological methods that mutant SOD1 accumulates inside the ER, where it forms insoluble high molecular weight species and interacts with the ER chaperone immunoglobulin-binding protein. These alterations are age- and region-specific, because they develop over the course of the disease and occur in the affected spinal cord but not in the nonaffected cerebellum in transgenic mutant SOD1 mice. Our results suggest a toxic mechanism for mutant SOD1 by which this ubiquitously expressed pathogenic protein could affect motor neuron survival and contribute to the selective motor neuronal degeneration in ALS.<\/jats:p>","DOI":"10.1073\/pnas.0509227103","type":"journal-article","created":{"date-parts":[[2006,4,4]],"date-time":"2006-04-04T20:34:38Z","timestamp":1144182878000},"page":"6025-6030","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":285,"title":["Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model"],"prefix":"10.1073","volume":"103","author":[{"given":"Hitoshi","family":"Kikuchi","sequence":"first","affiliation":[{"name":"Departments of *Neurology,"},{"name":"Department of Neurology, Kyushu University, Fukuoka 812-8582, 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