文章基本信息

标题：Prevention of Prion Propagation by Dehydrocholesterol Reductase Inhibitors in Cultured Cells and a Therapeutic Trial in Mice
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作者：Ken'ichi Hagiwara ; Yuko Nakamura ; Masahiro Nishijima 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：4
页码：835-838
DOI：10.1248/bpb.30.835
出版社：The Pharmaceutical Society of Japan
摘要：In prion diseases, the normal cellular form of prion protein (PrP^C) is converted into the disease-associated isoforms (PrP^Sc) which accumulate in the infected tissues. Although the precise mechanism of this conversion remains unsolved, drugs of various categories have been reported to reduce the accumulation of PrP^Sc in prion-infected cultured cells. We here show that AY-9944 (a 7-dehydrocholesterol reductase inhibitor) and U18666A (a 24-dehydrocholesterol reductase inhibitor) prevent PrP^Sc from accumulating in prion-infected mouse neuroblastoma cells (ScN2a), with an ED₅₀ of about 0.5 μ M and 10 n M , respectively. In order to evaluate the efficacy of these two inhibitors in vivo , C57BL/6J mice inoculated with mouse-adapted scrapie-prion received repetitive intraperitoneal injections of U18666A (10 mg/kg) or a mixture of U18666A (10 mg/kg) and AY-9944 (12 mg/kg). By contrast to the potent anti-prion effects observed in ScN2a cells, the in vivo trial was abortive with neither drug halting the progression of the disease.
关键词：prion;U18666A;AY-9944;desmosterol;7-dehydrocholesterol;lipid raft