Using budding yeast to screen for anti-prion drugs.

Abstract

Prions are misfolded proteins capable of propagating their altered conformation which are commonly considered as the causative agent of transmissible spongiform encephalopathies, a class of fatal neurodegenerative diseases. Currently, no treatment for prion-based diseases is available. Recently we have developed a rapid, yeast-based, two-step assay to screen for anti-prion drugs [1]. This new method allowed us to identify several compounds that are effective in vivo against budding yeast [PSI+] and [URE3] prions but also able to promote mammalian prion clearance in three different cell culture-based assays. Taken together, these results validate our method as an economic and efficient high-throughput screening approach to identify novel prion inhibitors or to carry on comprehensive structure-activity studies for already isolated anti-mammalian prion drugs. These results suggest furthermore that biochemical pathways controlling prion formation and/or maintenance are conserved from yeast to human and thus amenable to pharmacological and genetic analysis. Finally, it would be very interesting to test active drugs isolated using the yeast-based assay in models for other diseases (neurodegenerative or not) involving amyloid fibers like Huntington's, Parkinson's or Alzheimer's diseases.

• Authors: Déborah Tribouillard, Stéphane Bach, Fabienne Gug, Nathalie Desban, Vincent Beringue, Thibault Andrieu, Dominique Dormont, Hervé Galons, Hubert Laude, Didier Vilette, Marc Blondel
• Journal: Biotechnology journal (Biotechnol J) Vol. 1 Issue 1 Pg. 58-67 (Jan 2006) ISSN: 1860-6768 [Print] Germany
• PMID: 16892225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Technical Report)

Chemical References

• Peptide Termination Factors
• Prions
• SUP35 protein, S cerevisiae
• Saccharomyces cerevisiae Proteins
• Glutathione Peroxidase
• URE2 protein, S cerevisiae

Topics

• Biological Assay (methods)
• Glutathione Peroxidase
• Peptide Termination Factors
• Prions (antagonists & inhibitors, metabolism)
• Saccharomyces cerevisiae Proteins (metabolism)
• Saccharomycetales (drug effects, metabolism)
• Signal Transduction (drug effects, physiology)