Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation.
We report that lysosomotropic agents and cysteine protease inhibitors inhibited protease-resistant prion protein accumulation in scrapie-infected neuroblastoma 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 inhibitors of the formation of protease-resistant prion protein.
Doh-Ura
K
K
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. doh-ura@np.med.kyushu-u.ac.jp
Iwaki
T
T
Caughey
B
B
D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma; D018620:PrPSc Proteins / Q000187:drug effects* / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D018620:PrPSc Proteins; D007930:Leucine; D011796:Quinacrine; C108192:aloxistatin