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@ARTICLE{Stahl:263808,
      author       = {Stahl, Fabian and Schmitt, Ina and Denner, Philip and de
                      Boni, Laura and Wüllner, Ullrich and Breuer, Peter},
      title        = {{H}igh throughput compound screening in neuronal cells
                      identifies statins as activators of ataxin 3 expression.},
      journal      = {Scientific reports},
      volume       = {13},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2023-00893},
      pages        = {14911},
      year         = {2023},
      abstract     = {The spinocerebellar ataxias (SCA) comprise a group of
                      inherited neurodegenerative diseases. SCA3 is the most
                      common form, caused by the expansion of CAG repeats within
                      the ataxin 3 (ATXN3) gene. The mutation results in the
                      expression of an abnormal protein, containing long
                      polyglutamine (polyQ) stretches. The polyQ stretch confers a
                      toxic gain of function and leads to misfolding and
                      aggregation of ATXN3 in neurons. Thus, modulators of ATXN3
                      expression could potentially ameliorate the pathology in
                      SCA3 patients. 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 ATXN3 mRNA and protein levels which likely
                      results from direct binding of the activated sterol
                      regulatory element binding protein 1 (SREBP1) to the ATXN3
                      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.},
      keywords     = {Humans / Ataxin-3: genetics / Hydroxymethylglutaryl-CoA
                      Reductase Inhibitors: pharmacology / Neurons / Simvastatin /
                      Spinocerebellar Ataxias / Ataxin-3 (NLM Chemicals) /
                      Hydroxymethylglutaryl-CoA Reductase Inhibitors (NLM
                      Chemicals) / Simvastatin (NLM Chemicals)},
      cin          = {AG Wüllner / LAT},
      ddc          = {600},
      cid          = {I:(DE-2719)1011302 / I:(DE-2719)1040190},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      experiment   = {EXP:(DE-2719)LAT-20190308},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10492798},
      pubmed       = {pmid:37689718},
      doi          = {10.1038/s41598-023-41192-4},
      url          = {https://pub.dzne.de/record/263808},
}