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让酵母颤抖:酵母模型作为研究神经退行性疾病的工具

Making yeast tremble: yeast models as tools to study neurodegenerative disorders.

作者信息

Sherman Michael Y, Muchowski Paul J

机构信息

Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.

出版信息

Neuromolecular Med. 2003;4(1-2):133-46. doi: 10.1385/NMM:4:1-2:133.

Abstract

Genetic experiments in mice, which are indispensable for studying the molecular basis of neurological disorders, have certain limitations that include slow pace and high costs. It is therefore not surprising that in recent years numerous neurological diseases have been modeled in genetically tractable organisms, including Drosophila, Caenorhabditis elegans, and yeast. Yeast models in particular have a special advantage with respect to genome-wide experimental approaches as a result of the completed sequencing of the genome, the availability of a collection of precise deletion mutants of every gene in the genome, and the rapidly evolving databases of yeast protein-protein interactions and gene expression patterns. These large and easily accessible bodies of information, coupled with the ease with which yeast can be manipulated genetically, have led to dissection of novel mechanisms of neurodegenerative disorders. In this review, we discuss how studies in yeast models have already resulted in significant insights into the understanding of neurodegenerative disorders that include prion disease, Parkinson's disease, polyglutamine expansion disorders, Friedreich's ataxia, and Batten disease.

摘要

对于研究神经疾病的分子基础而言不可或缺的小鼠基因实验存在某些局限性,包括进展缓慢和成本高昂。因此,近年来众多神经疾病已在基因易处理的生物体中建立模型,包括果蝇、秀丽隐杆线虫和酵母,这并不令人惊讶。特别是酵母模型,由于基因组已完成测序、基因组中每个基因的精确缺失突变体集合可用,以及酵母蛋白质 - 蛋白质相互作用和基因表达模式的数据库迅速发展,在全基因组实验方法方面具有特殊优势。这些大量且易于获取的信息,再加上酵母易于进行基因操作,已促成对神经退行性疾病新机制的剖析。在本综述中,我们讨论酵母模型研究如何已经在对包括朊病毒病、帕金森病、多聚谷氨酰胺扩增疾病、弗里德赖希共济失调和巴顿病在内的神经退行性疾病的理解上带来了重要见解。

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