Pre-symptomatic detection of prions by cyclic amplification of protein misfolding
Pre-symptomatic detection of prions by cyclic amplification of protein misfolding
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DOI：
10.1016/j.febslet.2004.12.035
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发表时间：
2005-01-31
期刊：
影响因子：
3.5
通讯作者：
Tagliavini, F
中科院分区：
文献类型：
--
作者：
Soto, C;Anderes, L;Tagliavini, F
传染性海绵状脑病（TSE）是影响人类和动物的神经退行性疾病。目前，不可能在临床症状出现之前识别潜伏疾病的个体。我们研究了“蛋白质错误折叠循环扩增”（PMCA）技术在症状前阶段检测蛋白酶抗性疾病相关朊蛋白（PrPres）的有效性。PMCA允许在症状前仓鼠的大脑中检测PrPres，从而能够在接种后两周内明确识别感染动物。此外，PMCA能够从各种实验和天然TSE中扩增微量的PrPres。最后，PMCA允许在接种后32个月的实验感染奶牛中证明PrPres，该奶牛未显示临床体征，并且通过标准蛋白质印迹分析呈阴性。我们的研究结果表明，PMCA可能有助于开发超灵敏的诊断试验，以最大限度地减少TSE进一步传播的风险。(C)2004年欧洲生物化学学会联合会。Elsevier B.V.出版，保留所有权利。
Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders affecting humans and animals. At present, it is not possible to recognize individuals incubating the disease before the clinical symptoms appear. We investigated the effectiveness of the "Protein Misfolding Cyclic Amplification" (PMCA) technology to detect the protease-resistance disease-associated prion protein (PrPres) in pre-symptomatic stages. PMCA allowed detection of PrPres in the brain of pre-symptomatic hamsters, enabling a clear identification of infected animals as early as two weeks after inoculation. Furthermore, PMCA was able to amplify minute quantities of PrPres from a variety of experimental and natural TSEs. Finally, PMCA allowed the demonstration of PrPres in an experimentally infected cow 32 month post-inoculation, that did not show clinical signs and was negative by standard Western blot analysis. Our findings indicate that PMCA may be useful for the development of an ultra-sensitive diagnostic test to minimize the risk of further propagation of TSEs. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.