Nanoimaging for prion related diseases
Nanoimaging for prion related diseases
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DOI：
10.4161/pri.4.4.13125
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发表时间：
2010-10-01
期刊：
影响因子：
2.3
通讯作者：
Lyubchenko, Yuri L.
中科院分区：
文献类型：
--
作者：
Krasnoslobodtsev, Alexey V.;Portillo, Alexander M.;Lyubchenko, Yuri L.
Pron蛋白的错误折叠和聚集与许多神经退行性疾病有关，如CreutzFeldt-Jacob病(CJD)及其变种：库鲁病、Gerstmann-Straussler-Scheinker综合征和致命性家族性失眠。在Pron疾病中，感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，导致聚集体的形成，并最终导致神经退化。普恩现象并不局限于人类。在多种哺乳动物中存在多种与病毒相关的疾病，包括牛的牛海绵状脑病(BSE，也被称为“疯牛病”)。所有已知的Prion疾病，统称为可传播的海绵状脑病(TSE)，都是无法治疗和致命的。在一些真菌中也发现了Pron蛋白，在这些真菌中，它们决定了可遗传的特征。真菌中的Prion蛋白很容易获得，并为理解Pron现象的一般原理和哺乳动物Pron疾病的分子机制提供了一个强大的模型。目前，与普恩有关的几个基本问题仍未得到解答。例如，目前还不清楚普里恩是如何导致这种疾病的。其他未知因素包括传染性病原体的性质和结构以及普恩病毒如何复制。通常，Pron蛋白错误折叠成有感染性的构象的现象是很有意义的，这些构象能够通过聚集来传播它们的特性。尽管错误折叠和聚集至关重要，但目前对这些过程的分子机制知之甚少。尽管显然迫切需要研究导致错误折叠和聚集的分子机制，但传统方法的局限性阻碍了对这些单分子过程的详细描述。尽管一些问题仍未解决，但最近取得了很大进展，这主要是由于纳米成像工具的应用。纳米成像方法的使用显示了理解Pron现象的分子机制的巨大希望，可能导致对这些毁灭性疾病的早期诊断和有效治疗。这篇综述文章总结了最近的报道，这些报道通过使用纳米成像方法提高了我们对Prion现象的理解。
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.