Cashman N R
Affiliation: Faculty of Medicine, University of British Columbia, VancouverBC.
Can Commun Dis Rep. 2015 Aug 6;41(8):196-199. doi: 10.14745/ccdr.v41i08a03.
There is now good consensus that propagated protein misfolding is the underlying mechanism for the infectious prion diseases (Creutzfeldt-Jakob disease in humans, scrapie in sheep and goats, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer and elk). Over the past decade it has become increasingly clear that other diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis may progress via the same mechanism, involving a disease-specific polypeptide rather than the prion protein. Recent literature in these non-prion neurodegenerative diseases also points to the existence of multiple "strains" that express themselves differently in different contexts, resulting in different disease phenotypes. The probable cause of these neurodegenerative diseases is now referred to collectively as "propagated protein misfolding." Propagated protein misfolding raises many opportunities for new therapeutics and diagnostics. However, it also raises the theoretical risk of iatrogenic transmission, although experimental support for this notion is limited at present.
目前已形成广泛共识,即蛋白质的传播性错误折叠是传染性朊病毒疾病(人类的克雅氏病、绵羊和山羊的羊瘙痒症、牛的牛海绵状脑病以及鹿和麋鹿的慢性消耗病)的潜在机制。在过去十年中,越来越清楚的是,包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症在内的其他疾病可能通过相同机制进展,涉及特定疾病的多肽而非朊病毒蛋白。这些非朊病毒神经退行性疾病的最新文献也指出存在多种“毒株”,它们在不同情况下表现不同,导致不同的疾病表型。这些神经退行性疾病的可能病因现在统称为“传播性蛋白质错误折叠”。传播性蛋白质错误折叠为新的治疗方法和诊断带来了许多机会。然而,它也增加了医源性传播的理论风险,尽管目前这一观点的实验支持有限。