Ironside James W, Ritchie Diane L, Head Mark W
National CJD Research and Surveillance Unit, Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
National CJD Research and Surveillance Unit, Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.
Handb Clin Neurol. 2017;145:393-403. doi: 10.1016/B978-0-12-802395-2.00028-6.
The human prion diseases comprise Creutzfeldt-Jakob disease, variably protease-sensitive prionopathy, Gerstmann-Sträussler-Scheinker disease, fatal familial insomnia, and kuru. Each is a uniformly fatal rare neurodegenerative disease in which conformational changes in the prion protein are thought to be the central pathophysiologic event. The majority of cases of human prion diseases occur worldwide in the form of sporadic Creutzfeldt-Jakob disease and a minority of around 10-15% are associated with mutations of the prion protein gene, termed PRNP, in the forms of genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. Prion diseases are also transmissible and occur in iatrogenic and zoonotic forms (iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease respectively), adding a public health dimension to their management. Despite having a high public profile, human prion diseases are both rare and heterogeneous in their clinicopathologic phenotype, sometimes making a diagnosis challenging. A combined clinical, genetic, neuropathologic, and biochemical approach to diagnosis is therefore essential. The intensive study of these diseases continues to inform on neurodegenerative mechanisms and the role of protein misfolding in more common neurodegenerative diseases such as Parkinson disease and Alzheimer disease.
人类朊病毒病包括克雅氏病、可变蛋白酶敏感性朊病毒病、格斯特曼-施特劳斯勒-谢inker病、致死性家族性失眠症和库鲁病。每一种都是一种 uniformly fatal 罕见的神经退行性疾病，其中朊病毒蛋白的构象变化被认为是核心病理生理事件。人类朊病毒病的大多数病例在全球范围内以散发性克雅氏病的形式出现，少数约10-15%与朊病毒蛋白基因（称为PRNP）的突变有关，表现为遗传性克雅氏病、格斯特曼-施特劳斯勒-谢inker病和致死性家族性失眠症。朊病毒病也是可传播的，以医源性和人畜共患形式出现（分别为医源性克雅氏病和变异型克雅氏病），这为其管理增加了公共卫生层面的考量。尽管备受公众关注，但人类朊病毒病在临床病理表型上既罕见又具有异质性，有时诊断颇具挑战性。因此，采用临床、遗传、神经病理和生化相结合的诊断方法至关重要。对这些疾病的深入研究继续为神经退行性机制以及蛋白质错误折叠在帕金森病和阿尔茨海默病等更常见神经退行性疾病中的作用提供信息。 （注：原文中“uniformly fatal”不太明确准确含义，暂保留英文未翻译准确，根据语境推测可能是“一致致命的”之类意思）
