Telling G C, Parchi P, DeArmond S J, Cortelli P, Montagna P, Gabizon R, Mastrianni J, Lugaresi E, Gambetti P, Prusiner S B
Department of Neurology, University of California, San Francisco, CA 94143, USA.
Science. 1996 Dec 20;274(5295):2079-82. doi: 10.1126/science.274.5295.2079.
The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrPC) whereby it is converted into the pathologic isoform PrPSc. In fatal familial insomnia (FFI), the protease-resistant fragment of PrPSc after deglycosylation has a size of 19 kilodaltons, whereas that from other inherited and sporadic prion diseases is 21 kilodaltons. Extracts from the brains of FFI patients transmitted disease to transgenic mice expressing a chimeric human-mouse PrP gene about 200 days after inoculation and induced formation of the 19-kilodalton PrPSc fragment, whereas extracts from the brains of familial and sporadic Creutzfeldt-Jakob disease patients produced the 21-kilodalton PrPSc fragment in these mice. The results presented indicate that the conformation of PrPSc functions as a template in directing the formation of nascent PrPSc and suggest a mechanism to explain strains of prions where diversity is encrypted in the conformation of PrPSc.
朊病毒疾病的基本事件似乎是细胞朊蛋白（PrPC）发生构象变化，由此它被转化为病理性异构体PrPSc。在致死性家族性失眠症（FFI）中，去糖基化后PrPSc的蛋白酶抗性片段大小为19千道尔顿，而其他遗传性和散发性朊病毒疾病的该片段大小为21千道尔顿。FFI患者脑提取物在接种后约200天将疾病传播给表达嵌合人鼠PrP基因的转基因小鼠，并诱导形成19千道尔顿的PrPSc片段，而家族性和散发性克雅氏病患者脑提取物在这些小鼠中产生21千道尔顿的PrPSc片段。所呈现的结果表明，PrPSc的构象在指导新生PrPSc的形成中起模板作用，并提示了一种机制来解释朊病毒毒株，其中多样性编码在PrPSc的构象中。
