Details

Autor(en) / Beteiligte

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

Titel

A Cell-Based Assay for Aggregation Inhibitors as Therapeutics of Polyglutamine-Repeat Disease and Validation in Drosophila

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2003-05, Vol.100 (10), p.5950-5955

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2003

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.