NR AVCA
AU Tribouillard,D.; Bach,S.; Gug,F.; Desban,N.; Beringue,V.; Andrieu,T.; Dormont,D.; Galons,H.; Laude,H.; Vilette,D.; Blondel,M.
TI Using budding yeast to screen for anti-prion drugs
QU Biotechnology Journal 2006 Jan; 1(1): 58-67
PT journal article; technical report
AB 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.
MH Biological Assay/*methods; Prions/*antagonists & inhibitors/metabolism; Research Support, Non-U.S. Gov't; Saccharomyces cerevisiae Proteins/*metabolism; Saccharomycetales/*drug effects/*metabolism; Signal Transduction/drug effects/physiology
AD CNRS UMR7150, Amyloids and Cell Division Cycle Laboratory, Station Biologique, Roscoff, Bretagne, France.
SP englisch
PO Deutschland