Prion diseases are fatal neurodegenerative sporadic, inherited, or acquired disorders. In humans, Creutzfeldt-Jakob disease is the most studied prion disease. In animals, the most frequent prion diseases are scrapie in sheep and goat, bovine spongiform encephalopathy in cattle, and the emerging chronic wasting disease in wild and captive deer in North America. The hallmark of prion diseases is the deposition in the brain of PrPSc, an abnormal β-sheet-rich form of the cellular prion protein (PrPC) (Prusiner 1982). According to the prion hypothesis, PrPSc can trigger the autocatalytic conversion of PrPC into PrPSc, presumably in the presence of cofactors (lipids and small RNAs) that have been recently identified. In this review, we will come back to the original works that led to the discovery of prions and to the protein-only hypothesis proposed by Dr. Prusiner. We will then describe the recent reports on mammalian synthetic prions and recombinant prions that strongly support the protein-only hypothesis. The new concept of “deformed templating” regarding a new mechanism of PrPSc formation and replication will be exposed. The review will end with a chapter on the prion-like propagation of other neurodegenerative disorders, such as Alzheimer's and Parkinson's disease and tauopathies.
展开▼
机译:on病毒疾病是致命的神经退行性偶发性,遗传性或获得性疾病。在人类中,克雅氏病是研究最多的病毒病。在动物中,最常见的病毒病是绵羊和山羊的瘙痒病,牛的牛海绵状脑病,以及北美野生和圈养鹿的新兴慢性浪费病。病毒疾病的标志是PrP Sc sup>在大脑中的沉积,PrP Sc sup>是细胞β病毒蛋白(PrP C sup>)的富含β-折叠的异常形式(Prusiner 1982)。 。根据the病毒假说,PrP Sc sup>可以触发PrP C sup>到PrP Sc sup>的自动催化转化,大概在存在辅因子(脂质和脂质)的情况下。最近发现的小RNA)。在这篇评论中,我们将回到导致of病毒发现的原始著作以及普鲁西纳博士提出的仅蛋白质的假设。然后,我们将描述有关哺乳动物合成病毒和重组病毒的最新报道,这些报道强烈支持仅蛋白质的假说。将揭示有关PrP Sc sup>形成和复制的新机制的“变形模板”新概念。审查将以关于其他神经退行性疾病(如阿尔茨海默氏病和帕金森氏病和taophpathies)的the病毒样传播为结尾。
展开▼