Prusiner S B, Scott M R
Department of Neurology, University of California, San Francisco 94143, USA.
Annu Rev Genet. 1997;31:139-75. doi: 10.1146/annurev.genet.31.1.139.
Prions are unprecedented infectious pathogens that cause a group of invariably fatal, neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). The human prion disease Creutzfeldt-Jakob disease (CJD) generally presents as a progressive dementia, whereas scrapie of sheep and bovine spongiform encephalopathy (BSE) are manifest as ataxic illnesses. Prions are devoid of nucleic acid and seem to be composed exclusively of a modified isoform of PrP designated PrPSc. The normal, cellular PrP designated PrPC is converted into PrPSc through a process whereby some of its alpha-helical structure is converted into beta-sheet. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens with a nucleic acid genome, prions encipher strain-specific properties in the tertiary structure of PrPSc. Transgenetic studies argue that PrPSc acts as a template upon which PrPC is refolded into a nascent PrPSc molecule through a process facilitated by another protein.
朊病毒是前所未有的传染性病原体，通过一种全新的机制引发一系列无一例外致命的神经退行性疾病。朊病毒疾病可能表现为遗传性、传染性或散发性疾病，所有这些都涉及朊病毒蛋白（PrP）的修饰。人类朊病毒疾病克雅氏病（CJD）通常表现为进行性痴呆，而绵羊瘙痒病和牛海绵状脑病（BSE）则表现为共济失调性疾病。朊病毒不含核酸，似乎仅由一种称为PrPSc的PrP修饰异构体组成。正常的细胞PrP称为PrPC，通过其一些α-螺旋结构转化为β-折叠的过程转化为PrPSc。特定朊病毒的种类由其最后复制所在哺乳动物染色体PrP基因的序列编码。与具有核酸基因组的病原体不同，朊病毒在PrPSc的三级结构中编码毒株特异性特性。转基因研究表明，PrPSc充当模板，PrPC通过另一种蛋白质促进的过程重新折叠成新生的PrPSc分子。
