Recombinant prion protein induces a new transmissible prion disease in wild-type animals.
Recombinant prion protein induces a new transmissible prion disease in wild-type animals.
复制标题
重组prion蛋白在野生型动物中诱导了一种新的可传染性prion病。
DOI：
10.1007/s00401-009-0633-x
复制
发表时间：
2010-02
影响因子：
12.7
通讯作者：
Baskakov IV
中科院分区：
文献类型：
--
作者：
Makarava N;Kovacs GG;Bocharova O;Savtchenko R;Alexeeva I;Budka H;Rohwer RG;Baskakov IV
朊病毒病是一种神经退行性疾病，被认为是通过朊病毒蛋白的异常构象（PrPSc）传播的。先前的研究未能证明利用大肠杆菌产生的重组朊病毒蛋白（rPrP）可以在野生型动物中诱导朊病毒疾病。在这里，我们报道了在叙利亚仓鼠中接种全长rPrP后产生朊病毒传染性，rPrP已转化为交叉β-片淀粉样蛋白形式并经过退火。系列传播产生了一种具有高度独特的临床和神经病理特征的疾病表型。其中包括在脑和脊髓的脑膜下和室管膜下区域沉积大量的PrPSc斑块，海马和小脑的损伤非常轻微，尽管大脑中积累了大量的PrPSc，但在出现临床症状后疾病进展非常缓慢。与啮齿动物相比，人类和大型动物朊病毒病的临床病程更长。我们的研究证实了通过接种rPrP可以在野生型动物中诱导传染性朊病毒疾病，并为朊病毒疾病的研究提供了一种有价值的新模式。本文的在线版本（doi:10.1007/s00401-009-0633-x）包含补充材料，仅供授权用户使用。
Prion disease is a neurodegenerative malady, which is believed to be transmitted via a prion protein in its abnormal conformation (PrPSc). Previous studies have failed to demonstrate that prion disease could be induced in wild-type animals using recombinant prion protein (rPrP) produced in Escherichia coli. Here, we report that prion infectivity was generated in Syrian hamsters after inoculating full-length rPrP that had been converted into the cross-β-sheet amyloid form and subjected to annealing. Serial transmission gave rise to a disease phenotype with highly unique clinical and neuropathological features. Among them were the deposition of large PrPSc plaques in subpial and subependymal areas in brain and spinal cord, very minor lesioning of the hippocampus and cerebellum, and a very slow progression of disease after onset of clinical signs despite the accumulation of large amounts of PrPSc in the brain. The length of the clinical duration is more typical of human and large animal prion diseases, than those of rodents. Our studies establish that transmissible prion disease can be induced in wild-type animals by inoculation of rPrP and introduce a valuable new model of prion diseases. The online version of this article (doi:10.1007/s00401-009-0633-x) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
2.9
作者：
Nishina, Koren A.;Deleault, Nathan R.;Supattapone, Surachai
通讯作者：
Supattapone, Surachai
影响因子：
5.4
作者：
Frigg, R;Klein, MA;Aguzzi, A
通讯作者：
Aguzzi, A
影响因子：
4.8
作者：
Baskakov, IV;Legname, G;Cohen, FE
通讯作者：
Cohen, FE
影响因子：
4.8
作者：
Makarava, Natallia;Ostapchenko, Valeriy G.;Baskakov, Ilia V.
通讯作者：
Baskakov, Ilia V.
DOI：
10.1073/pnas.0702662104
发表时间：
2007-06-05
影响因子：
11.1
作者：
Deleault, Nathan R.;Harris, Brent T.;Supattapone, Surachai
通讯作者：
Supattapone, Surachai