Antihypertensive drug guanabenz is active in vivo against both yeast and mammalian prions.

ABSTRACT:

Background

Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans.

Methodology/principal findings

Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of alpha2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrP(Sc) clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on alpha2-adrenergic receptors as other chemically close ant

SUBMITTER: Tribouillard-Tanvier D 

PROVIDER: S-EPMC2291559 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature