Prusiner S B
Department of Neurology, University of California, San Francisco 94143.
Annu Rev Microbiol. 1994;48:655-86. doi: 10.1146/annurev.mi.48.100194.003255.
Enriching fractions from Syrian hamster (SHa) brain for scrapie prion infectivity led to the discovery of the prion protein (PrP). Prion diseases include scrapie of sheep, bovine spongiform encephalopathy (BSE) of cattle, as well as Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI) of humans. Discovery of mutations in the PrP genes of humans with familial CJD, GSS, and FFI established that prion diseases are both genetic and infectious. Many lines of evidence have converged to argue that infectious prions are composed largely, if not entirely, of PrPSc molecules. Mice overexpressing mutant and wild-type transgenes develop neurologic illnesses spontaneously and produce prions as demonstrated by serial transmission of disease in rodents after inoculation of brain extracts. Although these and many other findings argue that prions are devoid of nucleic acid, the molecular basis of prion strains remains enigmatic. The formation of PrPSc from PrPC is a posttranslational process involving the conversion of alpha-helices into beta-sheets. This conformational change in PrP appears to be the fundamental event that underlies prion propagation and the pathogenesis of prion diseases. The unique features of prion structure and propagation differentiate prions from all other transmissible pathogens.
从叙利亚仓鼠（SHa）脑中富集具有瘙痒病朊病毒感染性的组分，从而发现了朊病毒蛋白（PrP）。朊病毒疾病包括绵羊瘙痒病、牛的牛海绵状脑病（BSE）以及人类的克雅氏病（CJD）、格斯特曼-施特劳斯勒-谢inker病（GSS）和致死性家族性失眠症（FFI）。在患有家族性CJD、GSS和FFI的人类的PrP基因中发现突变，证实了朊病毒疾病既是遗传性的也是传染性的。许多证据都表明，传染性朊病毒如果不是完全由PrPSc分子组成，也主要由其组成。过表达突变型和野生型转基因的小鼠会自发出现神经疾病，并产生朊病毒，接种脑提取物后在啮齿动物中进行疾病的连续传播就证明了这一点。尽管这些以及许多其他发现都表明朊病毒不含核酸，但朊病毒株的分子基础仍然是个谜。从PrPC形成PrPSc是一个翻译后过程，涉及α螺旋向β折叠的转变。PrP的这种构象变化似乎是朊病毒传播和朊病毒疾病发病机制的根本事件。朊病毒结构和传播的独特特征使朊病毒与所有其他可传播病原体区分开来。
