Das Alvin S, Zou Wen-Quan
Departments of Pathology and Neurology, National Prion Disease Pathology Surveillance Center, National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Departments of Pathology and Neurology, National Prion Disease Pathology Surveillance Center, National Center for Regenerative Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
Clin Microbiol Rev. 2016 Jul;29(3):633-58. doi: 10.1128/CMR.00046-15.
Since the term protein was first coined in 1838 and protein was discovered to be the essential component of fibrin and albumin, all cellular proteins were presumed to play beneficial roles in plants and mammals. However, in 1967, Griffith proposed that proteins could be infectious pathogens and postulated their involvement in scrapie, a universally fatal transmissible spongiform encephalopathy in goats and sheep. Nevertheless, this novel hypothesis had not been evidenced until 1982, when Prusiner and coworkers purified infectious particles from scrapie-infected hamster brains and demonstrated that they consisted of a specific protein that he called a "prion." Unprecedentedly, the infectious prion pathogen is actually derived from its endogenous cellular form in the central nervous system. Unlike other infectious agents, such as bacteria, viruses, and fungi, prions do not contain genetic materials such as DNA or RNA. The unique traits and genetic information of prions are believed to be encoded within the conformational structure and posttranslational modifications of the proteins. Remarkably, prion-like behavior has been recently observed in other cellular proteins-not only in pathogenic roles but also serving physiological functions. The significance of these fascinating developments in prion biology is far beyond the scope of a single cellular protein and its related disease.
自1838年“蛋白质”一词首次被创造出来，且蛋白质被发现是纤维蛋白和白蛋白的重要组成部分以来，所有细胞蛋白质都被认为在植物和哺乳动物中发挥有益作用。然而，1967年，格里菲斯提出蛋白质可能是传染性病原体，并推测它们与羊瘙痒病有关，羊瘙痒病是一种在山羊和绵羊中普遍致命的传染性海绵状脑病。然而，直到1982年，这一新颖的假说才得到证实，当时普鲁辛纳及其同事从感染羊瘙痒病的仓鼠大脑中纯化出传染性颗粒，并证明它们由一种特定的蛋白质组成，他将其称为“朊病毒”。前所未有的是，传染性朊病毒病原体实际上源自其在中枢神经系统中的内源性细胞形式。与其他传染性病原体，如细菌、病毒和真菌不同，朊病毒不含DNA或RNA等遗传物质。朊病毒的独特特征和遗传信息被认为编码在蛋白质的构象结构和翻译后修饰中。值得注意的是，最近在其他细胞蛋白质中也观察到了类似朊病毒的行为——不仅在致病作用中，而且在发挥生理功能方面。朊病毒生物学中这些引人入胜的进展的意义远远超出了单一细胞蛋白质及其相关疾病的范畴。
