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We show that ALS patients and model mice display disease-related changes in spinal cord glycosphingolipids levels and in the enzymes that regulate their metabolism. Importantly, we demonstrate that inhibition of glycosphingolipid synthesis in ALS model mice exacerbated disease progression, whereas administration of GM3, a subtype of glycosphingolipids, slowed it, thus implicating glycosphingolipids as potentially important participants in ALS pathogenesis and potential targets for future drug development.<\/jats:p>","DOI":"10.1073\/pnas.1508767112","type":"journal-article","created":{"date-parts":[[2015,6,10]],"date-time":"2015-06-10T13:23:59Z","timestamp":1433942639000},"page":"8100-8105","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":132,"title":["Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis"],"prefix":"10.1073","volume":"112","author":[{"given":"James C.","family":"Dodge","sequence":"first","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Treleaven","sequence":"additional","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Cooper","sequence":"additional","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Channa","family":"Bao","sequence":"additional","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marissa","family":"Abraham","sequence":"additional","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Cromwell","sequence":"additional","affiliation":[{"name":"Rare Diseases Science, Genzyme, a Sanofi Company, Framingham, MA 01701;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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