TDP-43 toxicity in yeast.
TDP-43 toxicity in yeast.
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DOI：
10.1016/j.ymeth.2010.11.006
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发表时间：
2011-03
期刊：
影响因子：
4.8
通讯作者：
Gitler, Aaron D.
中科院分区：
文献类型：
--
作者：
Armakola, Maria;Hart, Michael P.;Gitler, Aaron D.
出芽酵母酿酒酵母是一种新兴工具，用于研究支撑几种与蛋白质错误折叠相关的人类神经退行性疾病的分子途径。肌萎缩侧索硬化症（ALS）是一种毁灭性的成年发病神经退行性疾病，主要影响运动神经元。最近已证明蛋白质TDP - 43在该疾病中起重要作用，然而TDP - 43导致发病的机制尚不清楚。为了探究导致TDP - 43异常积累的机制细节并发现治疗干预的潜在策略，我们采用了一个酵母TDP - 43蛋白病模型系统。这些研究使我们能够确定TDP - 43聚集和产生毒性所需的区域，并明确与ALS相关的TDP - 43突变形式的影响。我们还能够利用酵母遗传学的力量，通过高通量酵母遗传筛选来鉴定TDP - 43毒性的有效调节因子。在此，我们描述了为深入了解TDP - 43生物学及其在疾病中的作用而使用的方法和途径。这些方法很容易适用于其他神经退行性疾病相关蛋白质。
The budding yeast Saccharomyces cerevisiae is an emerging tool for investigating the molecular pathways that underpin several human neurodegenerative disorders associated with protein misfolding. Amyotrophic lateral sclerosis (ALS) is a devastating adult onset neurodegenerative disease primarily affecting motor neurons. The protein TDP-43 has recently been demonstrated to play an important role in the disease, however the mechanisms by which TDP-43 contributes to pathogenesis are unclear. To explore the mechanistic details that result in aberrant accumulation of TDP-43 and to discover potential strategies for therapeutic intervention, we employed a yeast TDP-43 proteinopathy model system. These studies allowed us to determine the regions of TDP-43 required for aggregation and toxicity and to define the effects of ALS-linked mutant forms of TDP-43. We have also been able to harness the power of yeast genetics to identify potent modifiers of TDP-43 toxicity using high-throughput yeast genetic screens. Here, we describe the methods and approaches that we have used in order to gain insight into TDP-43 biology and its role in disease. These approaches are readily adaptable to other neurodegenerative disease proteins.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
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DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
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3.1
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168.9
作者：
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