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

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

Research output: Contribution to journalArticle

134 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5950-5955
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number10
DOIs
Publication statusPublished - May 13 2003

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PC12 Cells
Drosophila
Huntington Disease
Therapeutics
Cell Culture Techniques
polyglutamine

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila. / Apostol, Barbara L.; Kazantsev, Alexsey; Raffioni, Simona; Illes, Katalin; Pallos, Judit; Bodai, L.; Slepko, Natalia; Bear, James E.; Gertler, Frank B.; Hersch, Steven; Housman, David E.; Marsh, J. Lawrence; Thompson, Leslie Michels.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 10, 13.05.2003, p. 5950-5955.

Research output: Contribution to journalArticle

Apostol, BL, Kazantsev, A, Raffioni, S, Illes, K, Pallos, J, Bodai, L, Slepko, N, Bear, JE, Gertler, FB, Hersch, S, Housman, DE, Marsh, JL & Thompson, LM 2003, 'A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 10, pp. 5950-5955. https://doi.org/10.1073/pnas.2628045100
Apostol, Barbara L. ; Kazantsev, Alexsey ; Raffioni, Simona ; Illes, Katalin ; Pallos, Judit ; Bodai, L. ; Slepko, Natalia ; Bear, James E. ; Gertler, Frank B. ; Hersch, Steven ; Housman, David E. ; Marsh, J. Lawrence ; Thompson, Leslie Michels. / A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 10. pp. 5950-5955.
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AU - Pallos, Judit

AU - Bodai, L.

AU - Slepko, Natalia

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AU - Gertler, Frank B.

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