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A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila

By Barbara L. Apostol, Alexsey Kazantsev, Simona Raffioni, Katalin Illes, Judit Pallos, Laszlo Bodai, Natalia Slepko, James E. Bear, Frank B. Gertler, Steven Hersch, David E. Housman, J. Lawrence Marsh and Leslie Michels Thompson


The formation of polyglutamine-containing aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation and may provide therapeutic benefit. We have developed inducible PC12 cell-culture models to screen for loss of visible aggregates. To test the validity of this approach, compounds that inhibit aggregation in the PC12 cell-based screen were tested in a Drosophila model of polyglutamine-repeat disease. The disruption of aggregation in PC12 cells strongly correlates with suppression of neuronal degeneration in Drosophila. Thus, the engineered PC12 cells coupled with the Drosophila model provide a rapid and effective method to screen and validate compounds

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2003
DOI identifier: 10.1073/pnas.2628045100
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Provided by: PubMed Central
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