Their Causes and Molecular Basis
Their Causes and Molecular Basis
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发表时间：
2001
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通讯作者：
J. Collinge
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作者：
J. Collinge
■ 摘要朊病毒病是一种传染性神经退行性疾病，包括人类的克雅氏病(CJD) 和动物的牛海绵状脑病(BSE) 和瘙痒病。朊病毒似乎主要或完全由宿主编码的糖蛋白、朊病毒蛋白的异常亚型组成。朊病毒增殖涉及将主要由β-螺旋结构组成的宿主细胞朊病毒蛋白募集到富含β-片层结构的疾病特异性亚型中。多种朊病毒株的存在很难用仅蛋白质感染因子来解释，但最近的研究表明，菌株特异性表型可以由不同的朊病毒蛋白构象和糖基化模式编码。蛋白质编码表型信息的能力具有重要的生物学意义。一种新型人类朊病毒疾病——变异型克雅氏病的出现，以及明确的实验证据表明该疾病是由接触疯牛病引起的，这凸显了了解朊病毒传播的分子基础、发病机制和限制哺乳动物间传播的障碍的必要性。目前尚不清楚未来几年是否会出现变异型克雅氏病的大规模流行。
■ Abstract Prion diseases are transmissible neurodegenerative conditions that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) and scrapie in animals. Prions appear to be composed principally or entirely of abnormal isoforms of a host-encoded glycoprotein, prion protein. Prion propagation involves recruitment of host cellular prion protein, composed primarily of -helical structure, into a disease specific isoform rich in -sheet structure. The existence of multiple prion strains has been difficult to explain in terms of a protein-only infections agent, but recent studies suggest that strain specific phenotypes can be encoded by different prion protein conformations and glycosylation patterns. The ability of a protein to encode phenotypic information has important biological implications. The appearance of a novel human prion disease, variant CJD, and the clear experimental evidence that it is caused by exposure to BSE has highlighted the need to understand the molecular basis of prion propagation, pathogenesis, and the barriers limiting intermammalian transmission. It is unclear if a large epidemic of variant CJD will occur in the years ahead.