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U.S.A."],"published-print":{"date-parts":[[2021,11,23]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Machado\u2013Joseph disease (MJD) is an incurable neurodegenerative disorder caused by a mutation in the ataxin-3 protein, which becomes toxic and induces cerebellar degeneration and motor impairments. Disturbances in the protein modification\n                    <jats:italic>O<\/jats:italic>\n                    -GlcNAcylation, catalyzed by the enzyme\n                    <jats:italic>O<\/jats:italic>\n                    -GlcNAc transferase (OGT), have been linked to neurodegeneration, but its potential involvement in MJD remains elusive. By analyzing MJD cells and animal models, we demonstrate altered levels of OGT in MJD, further identifying this enzyme as a substrate of ataxin-3. Targeting OGT reduced ataxin-3 toxicity, improving the motor phenotype of an MJD animal model. Our results unveiled a physiological interplay between ataxin-3 and OGT, highlighting OGT as a potential therapeutic target in this deadly condition.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2025810118","type":"journal-article","created":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T16:40:14Z","timestamp":1637080814000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":10,"title":["Pathophysiological interplay between\n                    <i>O<\/i>\n                    -GlcNAc transferase and the Machado\u2013Joseph disease protein ataxin-3"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-5470","authenticated-orcid":false,"given":"Priscila","family":"Pereira Sena","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of T\u00fcbingen, T\u00fcbingen 72076, Germany;"},{"name":"Center for Rare Diseases, University of 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