Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation

We report that lysosomotropic agents and cysteine protease inhibitors inhib ited protease resistant prion protein accumulation in scrapie-infected neur oblastoma cells. The inhibition occurred without either apparent effects on normal prion protein biosynthesis or turnover or direct interactions with prion protein molecules. The findings introduce two new classes of inhibito rs of the formation of protease-resistant prion protein.