School of Life Science and Technology, China Pharmaceutical University, Nanjing 21009, China.
Acta Biochim Biophys Sin (Shanghai). 2013 Jun;45(6):442-51. doi: 10.1093/abbs/gmt037. Epub 2013 Apr 4.
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 prion disease is the conformational conversion of the host-derived cellular prion protein (PrP(C)) into a misfolded form (scrapie PrP, PrP(Sc)). Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins. Both the prion oligomer and PrP(Sc) are rich in β-sheet structure and resistant to the proteolysis of proteinase K. The prion oligomer is soluble in physiologic environments whereas PrP(Sc) 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 PrP(Sc), implying that prion oligomers 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.
朊病毒病，也称为传染性海绵状脑病，是致命的神经退行性疾病。根据“蛋白构象改变唯一假说”，朊病毒病发病机制中的关键分子事件是宿主来源的细胞朊蛋白（PrP(C)）构象转换为错误折叠形式（瘙痒病朊蛋白，PrP(Sc)）。越来越多的证据表明，最具传染性的因素是由朊蛋白形成的更小的亚纤维寡聚物。朊蛋白寡聚物和 PrP(Sc)富含β-折叠结构，并且对蛋白酶 K 的蛋白水解作用具有抗性。朊蛋白寡聚物在生理环境中是可溶的，而 PrP(Sc)是不可溶的。不同的朊蛋白寡聚物在不同条件下形成。与 PrP(Sc)的纤维形式相比，朊蛋白寡聚物在体外和体内均表现出更强的神经毒性，这表明朊蛋白寡聚物可能是攻击朊病毒病的潜在药物靶点。本文描述了朊蛋白寡聚物的最新实验证据，特别关注朊蛋白寡聚物的形成及其神经毒性。
