| Literature DB >> 12730384 |
Barbara L Apostol1, 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, Leslie Michels Thompson.
Abstract
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.Entities:
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Year: 2003 PMID： 12730384 PMCID： PMC156307 DOI： 10.1073/pnas.2628045100
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205