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Mini-Review
Antiprion Drugs as Chemical Tools to Uncover Mechanisms of Prion Propagation
Deborah Tribouillard, Fabienne Gug, Hervé Galons, Stéphane Bach, Sven J. Saupe and Marc Blondel
volume 1 | issue 1
January/February/March 2007We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
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A number of drugs active against prions either in vitro, in cellular systems or in vivo in animal models have been isolated in various screening assays. In this minireview, we would like to suggest, that in addition to their direct interest as potential therapeutic agents, these molecules could be used as original research tools to understand prion propagation. The use of antiprion compounds as tool to understand fundamentals of prion propagation relies on reverse screening approaches. These global genetic and/or biochemical approaches aim to identify the intracellular target(s) and mechanism of action of the drugs. Once those are known, the biological activity of the compounds can be optimized on a rational basis, their potential side effects understood and minimized. In vitro enzyme-based screening assays can then be designed to allow discovery of new, more potent and selective molecules. Here we describe the main comprehensive biochemical and genetical approaches to realize reverse screening approaches based on antiprion drugs. We will finish by discussing the interest of using drug inactivation of specific targets as a substitute to genetic inactivation.
Authors
Deborah Tribouillard
CNRS, Roscoff, France
Fabienne Gug
Université René Descartes, Paris, France
Hervé Galons
Université René Descartes, Paris, France
Stéphane Bach
CNRS, Roscoff, France
Sven J. Saupe
CNRS Université de Bordeaux 2
Marc Blondel
INSERM/UBO Medical School, CHU of Brest, Brest, France
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.