Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs

Déborah Tribouillard-Tanvier
Suzana Dos Reis
Fabienne Gug
Cécile Voisset

Déborah Tribouillard-Tanvier;Suzana Dos Reis;Fabienne Gug;Cécile Voisset;Vincent Béringue;Raimon Sabate;Ema Kikovska;Nicolas Talarek;Stéphane Bach;Chenhui Huang;Nathalie Desban;Sven J. Saupe;Surachai Supattapone;Jean-Yves Thuret;Stéphane Chédin;Didier Vilette;Hervé Galons;Suparna Sanyal;Marc Blondel;Stefan Wölfl

Abstract

Background6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.Methodology/Principal FindingsHere we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demo