A yeast-based assay to isolate drugs active against mammalian prions

Methods. 2006 May;39(1):72-7. doi: 10.1016/j.ymeth.2006.04.005.

Abstract

Recently, we have developed a yeast-based (Saccharomyces cerevisiae) assay to isolate drugs active against mammalian prions. The initial assumption was that mechanisms controlling prion appearance and/or propagation could be conserved from yeast to human, as it is the case for most of the major cell biology regulatory mechanisms. Indeed, the vast majority of drugs we isolated as active against both [PSI(+)] and [URE3] budding yeast prions turned out to be also active against mammalian prion in three different mammalian cell-based assays. These results strongly argue in favor of common prion controlling mechanisms conserved in eukaryotes, thus validating our yeast-based assay and also the use of budding yeast to identify antiprion compounds and to study the prion world.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical / methods
  • False Positive Reactions
  • Glutathione Peroxidase
  • Methyltransferases / antagonists & inhibitors
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Peptide Termination Factors
  • PrPSc Proteins / antagonists & inhibitors
  • PrPSc Proteins / genetics
  • PrPSc Proteins / metabolism
  • Prions / antagonists & inhibitors*
  • Prions / genetics
  • Prions / metabolism
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / antagonists & inhibitors
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Anti-Infective Agents
  • Peptide Termination Factors
  • PrPSc Proteins
  • Prions
  • SUP35 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Glutathione Peroxidase
  • URE2 protein, S cerevisiae
  • Methyltransferases
  • delta 24-sterol methyltransferase