Bioactivity profiling with parallel mass spectrometry reveals an assemblage of green tea metabolites affording protection against human huntingtin and alpha-synuclein toxicity.
Bioactivity profiling with parallel mass spectrometry reveals an assemblage of green tea metabolites affording protection against human huntingtin and alpha-synuclein toxicity.
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使用平行质谱法进行的生物活性分析揭示了绿茶代谢物的组合，可提供针对人类亨廷顿蛋白和 α-突触核蛋白毒性的保护。
DOI：
10.1021/jf072241x
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发表时间：
2007
影响因子：
6.1
通讯作者：
Cichewicz,RobertH
中科院分区：
文献类型：
--
作者：
Williams,RussellB;Gutekunst,WillR;Joyner,PMatthew;Duan,Wenzhen;Li,Qing;Ross,ChristopherA;Williams,ToddD;Cichewicz,RobertH
异常蛋白聚集和错误折叠是许多神经退行性疾病的关键病理特征，包括亨廷顿氏病和帕金森病。提供保护免受与易聚集的神经退行性蛋白相关的毒性的化合物可能应用于治疗多种疾病。采用平行电喷雾电离质谱筛选的高通量生物测定系统已被设计用于对毫克量的天然产品提取物（包括膳食物质）进行关键评估，用于与治疗人类神经退行性疾病相关的药理化合物。利用酿酒酵母基因工程表达突变的人类亨廷顿蛋白和α-突触核蛋白，我们能够鉴定出保护细胞免受这些蛋白毒性影响的提取物和化合物。应用这种筛选模式，我们确定了一种具有生物活性的绿茶提取物含有一组儿茶素，这些儿茶素分别具有抗亨廷顿蛋白和α-突触核蛋白毒性的保护作用。
Aberrant protein aggregation and misfolding are key pathological features of many neurodegenerative disorders, including Huntington’s and Parkinson’s diseases. Compounds that offer protection from toxicity associated with aggregation-prone neurodegenerative proteins may have applications for the treatment of a multitude of disorders. A high-throughput bioassay system with parallel electrospray ionization mass spectrometry screening has been designed for critical evaluation of milligram quantities of natural product extracts, including dietary substances, for compounds of pharmacological relevance to the treatment of human neurodegenerative diseases. UsingSaccharomyces cerevisiaestrains engineered to express mutant human huntingtin and α-synuclein, we are able to identify extracts and compounds that protect cells from toxicity associated with these proteins. Applying this screening paradigm, we determined that a bioactive green tea extract contains an assemblage of catechins that were individually characterized for their respective protective effects against huntingtin and α-synuclein toxicity.