prion 疾病,也作为能递送的海绵状的 encephalopathies 知道,是致命的 neurodegenerative 混乱。根据蛋白质仅仅假设,在 prion 疾病的致病的关键分子的事件是导出主人的细胞的 prion 蛋白质(PrPC ) 的 conformational 变换进一种错误褶层形式(scrapie PrP, PrPSc ) 。增加的证据证明了最传染的因素是 prion 蛋白质形成的更小的 subfibrillar oligomers。prion oligomer 和 PrPSc 富于表结构并且对朊酶 K 的解朊作用抵抗。而 PrPSc 是不可溶解的, prion oligomer 在生理的环境是可溶的。各种各样的 prion oligomers 处于不同条件被形成。Prion oligomers 比 PrPSc 的纤丝状的形式在 vitro 并且在 vivo 展出了更多的 neurotoxicity,暗示 prion oligomers 能是为攻击 prion 疾病的潜在的药目标。在这篇文章,我们关于 prion oligomers 描述最近的试验性的证据,与 prion oligomer 形成和它的 neurotoxicity 的一个特殊焦点。
The prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. According to the 'protein only' hypothesis, the key molecular event in the pathogenesis of priori disease is the conformational conversion of the host-derived cellular prion protein (PrPc) into a misfolded form (scrapie PrP, prpSC). Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins. Both the prion oligomer and PrPsc are rich in β-sheet structure and resistant to the proteolysis of pro- teinase K. The prion oligomer is soluble in physiologic environments whereas PrPsc is insoluble. Various prion oligomers are formed in different conditions. Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrPsc, implying that prion oligo- mers could be potential drug targets for attacking prion diseases. In this article, we describe recent experimental evidence regarding prion oligomers, with a special focus on prion oligomer formation and its neurotoxicity.