Saccharomyces cerevisiae in neuroscience: how unicellular organism helps to better understand prion protein?
Saccharomyces cerevisiae in neuroscience: how unicellular organism helps to better understand prion protein?
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神经科学中的酿酒酵母：单细胞生物如何帮助更好地理解朊病毒蛋白？
DOI：
10.4103/1673-5374.293137
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发表时间：
2021-03
影响因子：
6.1
通讯作者：
Ishikawa T
中科院分区：
文献类型：
--
作者：
Ishikawa T
面包师酵母(S.)酿酒酵母是一种广泛应用于生命科学研究的单细胞真核模式生物。酿酒酵母是一种单细胞生物，在神经科学中的应用存在明显的局限性。然而，人们对酵母蛋白进行了广泛的研究，并已知它们与哺乳动物蛋白或其他在阿尔茨海默病、帕金森病或亨廷顿病的发病机制中发现的淀粉样蛋白有一些共同的特征。因此，酿酒酵母被广泛用于研究蛋白质在纤维素中的聚集特性及其繁殖的基础研究。最近，一项以酵母为基础的研究发现，哺乳动物的Prion蛋白和淀粉样蛋白β1-42的某些区域能够诱导和繁殖酵母Prion。这是一个例子，表明进化上相距遥远的生物具有共同的机制，这些共同的机制导致了Pron蛋白的结构转换，使酵母细胞成为研究哺乳动物Pron蛋白的有用系统。酿酒酵母也被用来设计从化学文库中筛选抗病毒化合物的新系统。基于酵母的检测方法维护成本低，对研究人员来说也是安全的，这使得它们成为在与感染了普恩病毒的哺乳动物细胞接触的系统进一步鉴定之前进行初步筛选的非常好的选择。本文对近年来发展起来的经典红/白菌落试验和基于酵母的筛选试验进行了综述。计算分析和使用酵母蛋白进行的研究迫使我们认为，蛋白广泛存在于自然界中。事实上，过去几年给我们带来了几个例子，表明哺乳动物的Pron蛋白不再是一种特殊的蛋白质--似乎更好地了解整个自然界的Prion蛋白可能有助于我们治疗Pron疾病和其他与淀粉样蛋白相关的疾病。
The baker’s yeast Saccharomyces (S.) cerevisiae is a single-celled eukaryotic model organism widely used in research on life sciences. Being a unicellular organism, S. cerevisiae has some evident limitations in application to neuroscience. However, yeast prions are extensively studied and they are known to share some hallmarks with mammalian prion protein or other amyloidogenic proteins found in the pathogenesis of Alzheimer’s, Parkinson’s, or Huntington’s diseases. Therefore, the yeast S. cerevisiae has been widely used for basic research on aggregation properties of proteins in cellulo and on their propagation. Recently, a yeast-based study revealed that some regions of mammalian prion protein and amyloid β1–42 are capable of induction and propagation of yeast prions. It is one of the examples showing that evolutionarily distant organisms share common mechanisms underlying the structural conversion of prion proteins making yeast cells a useful system for studying mammalian prion protein. S. cerevisiae has also been used to design novel screening systems for anti-prion compounds from chemical libraries. Yeast-based assays are cheap in maintenance and safe for the researcher, making them a very good choice to perform preliminary screening before further characterization in systems engaging mammalian cells infected with prions. In this review, not only classical red/white colony assay but also yeast-based screening assays developed during last year are discussed. Computational analysis and research carried out using yeast prions force us to expect that prions are widely present in nature. Indeed, the last few years brought us several examples indicating that the mammalian prion protein is no more peculiar protein – it seems that a better understanding of prion proteins nature-wide may aid us with the treatment of prion diseases and other amyloid-related medical conditions.
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