PLoS Pathog：科学家首次成功合成朊病毒

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图片来源：www.mnn.com

有时为了理解某些事物的发生机制，我们就需要对其进行重建，这对于朊病毒而言也是如此，近日，来自米兰BESTA研究所的研究人员就通过研究成功组装产生了人工的朊病毒，与此同时研究者还设计了一种方法来合成朊病毒；实验室检测结果表明，合成性的朊病毒可以和真正的朊病毒表现出相似的生物学特性，相关研究结果发表于国际杂志PLoS Pathogens上。

文章中，研究人员Giuseppe Legname指出，这项研究将帮助我们理解朊病毒引发疾病，比如疯牛病、克雅二氏症等疾病的分子机制；合成性的朊病毒可以帮助研究人员对实验中的致病性行为进行精准地控制，而对天然朊病毒进行操作就没有这么简单了，因为天然朊病毒非常复杂且具有异质性。

研究人员可以很容易地控制合成性朊病毒的异质性及结构特性，而且这些合成性的病毒还会表现出和天然病毒一样的序列；研究者的最终目标就是鉴别如何阻断朊病毒的感染，并且开发出新型疗法来抵御相关疾病的发生。

这项研究中，研究人员Legname及其同事首次合成了小鼠的朊病毒，并且鉴别出了朊病毒引发小鼠致病的分子机理，而这或许和天然朊病毒的致病机理相当，当科学家们对朊病毒特性分析时他们发现合成的朊病毒同引发疯牛病及克雅氏病的天然朊病毒非常相似。

研究人员最后表示，我们的研究一直在不断深入地进行，未来我们或许也将对人类天然朊病毒进行研究，这对于开发朊病毒引发的人类神经变性疾病的新型疗法或带来一定帮助；目前研究人员正在考虑是否可以把引发阿尔兹海默氏症的淀粉样蛋白，或引发帕金森疾病的关键分子进行合成，这或许也可以帮助开发新型疗法来治疗诸如阿尔兹海默氏症样的神经变性疾病。

来源：生物谷

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Synthetic prions with novel strain-specified properties

Fabio Moda , Thanh-Nhat T. Le , Suzana Aulić, Edoardo Bistaffa, Ilaria Campagnani, Tommaso Virgilio, Antonio Indaco, Luisa Palamara, Olivier Andréoletti, Fabrizio Tagliavini, Giuseppe Legname

Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrPSc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrPSc were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties.

http://journals.plos.org/plospat ... ournal.ppat.1005354