Comparison of protease-resistant prion protein inhibitors in cell cultures infected with two strains of mouse and sheep scrapie
Comparison of protease-resistant prion protein inhibitors in cell cultures infected with two strains of mouse and sheep scrapie
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DOI：
10.1016/j.neulet.2005.06.053
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发表时间：
2005-11-11
影响因子：
2.5
通讯作者：
Caughey, B
中科院分区：
文献类型：
--
作者：
Kocisko, DA;Engel, AL;Caughey, B
传染性海绵状脑病(TSE)是一种致命性神经退行性疾病。TSE干预的一个主要治疗目标是一种称为PrPSc或PrP-res的抗蛋白酶形式的PrP蛋白。对小鼠瘙痒病感染细胞培养的体外测试发现，许多PrP-RES抑制剂在体内也具有活性。在这里，我们确定了两个品系的小鼠瘙痒病PrP-Res的32种新的抑制剂。此外，为了研究这些和其他PrP-RES抑制剂的物种特异性，我们建立了一种基于绵羊瘙痒病慢性感染的Rov9细胞的高通量细胞培养方法。在Rov9细胞中测试的32种小鼠PrP-RES抑制剂中，只有6种显示出对绵羊PrP-RES的抑制活性。对小鼠和绵羊PrP-Res形成的三种最有效的抑制物(在
The transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases. A primary therapeutic target for TSE intervention has been a protease-resistant form of prion protein known as PrPSc or PrP-res. In vitro testing of mouse scrapie-infected cell cultures has identified many PrP-res inhibitors that also have activity in vivo. Here we identify 32 new inhibitors of two strains of mouse scrapie PrP-res. Furthermore, to investigate the species-specificity of these and other PrP-res inhibitors, we have developed a high-throughput cell culture assay based on Rov9 cells chronically-infected with sheep scrapie. Of 32 inhibitors of murine PrP-res that were also tested in the Rov9 cells, only six showed inhibitory activity against sheep PrP-res. The three most potent inhibitors of both murine and ovine PrP-res formation (with 50% inhibition at