Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
Prion. 2010 Oct-Dec;4(4):265-74. doi: 10.4161/pri.4.4.13125. Epub 2010 Oct 23.
Misfolding and aggregation of prion proteins is linked to a number of neurodegenerative disorders such as Creutzfeldt-Jacob disease (CJD) and its variants: Kuru, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. In prion diseases, infectious particles are proteins that propagate by transmitting a misfolded state of a protein, leading to the formation of aggregates and ultimately to neurodegeneration. Prion phenomenon is not restricted to humans. There are a number of prion-related diseases in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle. All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal. Prion proteins were also found in some fungi where they are responsible for heritable traits. Prion proteins in fungi are easily accessible and provide a powerful model for understanding the general principles of prion phenomenon and molecular mechanisms of mammalian prion diseases. Presently, several fundamental questions related to prions remain unanswered. For example, it is not clear how prions cause the disease. Other unknowns include the nature and structure of infectious agent and how prions replicate. Generally, the phenomenon of misfolding of the prion protein into infectious conformations that have the ability to propagate their properties via aggregation is of significant interest. Despite the crucial importance of misfolding and aggregation, very little is currently known about the molecular mechanisms of these processes. While there is an apparent critical need to study molecular mechanisms underlying misfolding and aggregation, the detailed characterization of these single molecule processes is hindered by the limitation of conventional methods. Although some issues remain unresolved, much progress has been recently made primarily due to the application of nanoimaging tools. The use of nanoimaging methods shows great promise for understanding the molecular mechanisms of prion phenomenon, possibly leading toward early diagnosis and effective treatment of these devastating diseases. This review article summarizes recent reports which advanced our understanding of the prion phenomenon through the use of nanoimaging methods.
朊病毒蛋白的错误折叠和聚集与许多神经退行性疾病有关，如克雅氏病（CJD）及其变体：库鲁病、格斯特曼-施特劳斯勒-谢因克综合征和致命家族性失眠症。在朊病毒疾病中，传染性颗粒是通过传递蛋白质的错误折叠状态来传播的蛋白质，导致聚集的形成，最终导致神经退行性变。朊病毒现象不仅限于人类。在包括牛海绵状脑病（BSE，也称为“疯牛病”）在内的多种哺乳动物中，有许多与朊病毒相关的疾病。所有已知的朊病毒疾病统称为传染性海绵状脑病（TSEs），均无法治愈且致命。朊病毒蛋白也存在于某些真菌中，在真菌中它们负责遗传特征。真菌中的朊病毒蛋白易于获得，为理解朊病毒现象的一般原理和哺乳动物朊病毒疾病的分子机制提供了有力的模型。目前，与朊病毒相关的几个基本问题仍未得到解答。例如，不清楚朊病毒如何引起疾病。其他未知因素包括传染性病原体的性质和结构以及朊病毒如何复制。一般来说，朊病毒蛋白错误折叠成具有传染性构象的现象以及通过聚集传播其特性的能力引起了人们的极大兴趣。尽管错误折叠和聚集现象至关重要，但目前对这些过程的分子机制知之甚少。尽管明显迫切需要研究错误折叠和聚集的分子机制，但由于常规方法的限制，这些单个分子过程的详细特征描述受到阻碍。尽管一些问题仍未解决，但由于纳米成像工具的应用，最近取得了很大进展。纳米成像方法的使用有望为理解朊病毒现象的分子机制提供帮助，可能会导致这些毁灭性疾病的早期诊断和有效治疗。本文综述了最近的一些报告，这些报告通过使用纳米成像方法，提高了我们对朊病毒现象的理解。
