Outeiro Tiago Fleming, Giorgini Flaviano
Whitehead Institute for Biomedical Research, MIT, Cambridge, MA, USA.
Biotechnol J. 2006 Mar;1(3):258-69. doi: 10.1002/biot.200500043.
The high degree of conservation of cellular and molecular processes between the budding yeast Saccharomyces cerevisiae and higher eukaryotes have made it a valuable system for numerous studies of the basic mechanisms behind devastating illnesses such as cancer, infectious disease, and neurodegenerative disorders. Several studies in yeast have already contributed to our basic understanding of cellular dysfunction in both Huntington's and Parkinson's disease. Functional genomics approaches currently being undertaken in yeast may lead to novel insights into the genes and pathways that modulate neuronal cell dysfunction and death in these diseases. In addition, the budding yeast constitutes a valuable system for identification of new drug targets, both via target-based and non-target-based drug screening. Importantly, yeast can be used as a cellular platform to analyze the cellular effects of candidate compounds, which is critical for the development of effective therapeutics. While the molecular mechanisms that underlie neurodegeneration will ultimately have to be tested in neuronal and animal models, there are several distinct advantages to using simple model organisms to elucidate fundamental aspects of protein aggregation, amyloid toxicity, and cellular dysfunction. Here, we review recent studies that have shown that amyloid formation by disease-causing proteins and many of the resulting cellular deficits can be faithfully recapitulated in yeast. In addition, we discuss new yeast-based techniques for screening candidate therapeutic compounds for Huntington's and Parkinson's diseases.
出芽酵母酿酒酵母与高等真核生物之间细胞和分子过程的高度保守性，使其成为研究癌症、传染病和神经退行性疾病等毁灭性疾病背后基本机制的众多研究的宝贵系统。酵母中的多项研究已经有助于我们对亨廷顿舞蹈病和帕金森病中细胞功能障碍的基本理解。目前在酵母中进行的功能基因组学方法可能会为调节这些疾病中神经元细胞功能障碍和死亡的基因及信号通路带来新的见解。此外，出芽酵母构成了一个通过基于靶点和非基于靶点的药物筛选来鉴定新药物靶点的宝贵系统。重要的是，酵母可用作细胞平台来分析候选化合物的细胞效应，这对有效治疗方法的开发至关重要。虽然神经退行性变背后的分子机制最终必须在神经元和动物模型中进行测试，但使用简单模型生物来阐明蛋白质聚集、淀粉样毒性和细胞功能障碍的基本方面有几个明显的优势。在这里，我们回顾了最近的研究，这些研究表明致病蛋白形成淀粉样蛋白以及许多由此导致的细胞缺陷可以在酵母中如实地重现。此外，我们讨论了用于筛选亨廷顿舞蹈病和帕金森病候选治疗化合物的基于酵母的新技术。
