Using budding yeast to screen for anti-prion drugs

Biotechnol J. 2006 Jan;1(1):58-67. doi: 10.1002/biot.200500001.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Technical Report

MeSH terms

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


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