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Therefore, we generated a CRISPR\/Cas9 modified ATXN3-Exon4-Luciferase (ATXN3-LUC) genomic fusion- and control cell lines to perform a reporter cell line-based high-throughput screen comprising 2640 bioactive compounds, including the FDA approved drugs. We found no unequivocal inhibitors of, but identified statins as activators of the LUC signal in the ATXN3-LUC screening cell line. We further confirmed that Simvastatin treatment of wild type SK-N-SH cells increases <jats:italic>ATXN3<\/jats:italic> mRNA and protein levels which likely results from direct binding of the activated sterol regulatory element binding protein 1 (SREBP1) to the <jats:italic>ATXN3<\/jats:italic> promotor. Finally, we observed an increase of normal and expanded ATXN3 protein levels in a patient-derived cell line upon Simvastatin treatment, underscoring the potential medical relevance of our findings.<\/jats:p>","DOI":"10.1038\/s41598-023-41192-4","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T15:01:25Z","timestamp":1694271685000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High throughput compound screening in neuronal cells identifies statins as activators of ataxin 3 expression"],"prefix":"10.1038","volume":"13","author":[{"given":"Fabian","family":"Stahl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Denner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"de Boni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ullrich","family":"W\u00fcllner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,9,9]]},"reference":[{"key":"41192_CR1","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1212\/wnl.28.7.703","volume":"28","author":"P Coutinho","year":"1978","unstructured":"Coutinho, P. & Andrade, C. 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