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细胞死亡分析在药物研发中的应用。

Cell death assays for drug discovery.

机构信息

INSERM, U848, F-94805 Villejuif, France.

出版信息

Nat Rev Drug Discov. 2011 Mar;10(3):221-37. doi: 10.1038/nrd3373.

Abstract

Cell death has an important role in many human diseases, and strategies aimed at modulating the associated pathways have been successfully applied to treat various disorders. Indeed, several clinically promising cytotoxic and cytoprotective agents with potential applications in cancer, ischaemic and neurodegenerative diseases have recently been identified by high-throughput screening (HTS), based on appropriate cell death assays. Given that different cell death modalities may be dysregulated in different diseases, it is becoming increasingly clear that such assays need to not only quantify the extent of cell death, but they must also be able to distinguish between the various pathways. Here, we systematically describe approaches to accurately quantify distinct cell death pathways, discuss their advantages and pitfalls, and focus on those techniques that are amenable to HTS.

摘要

细胞死亡在许多人类疾病中起着重要作用,旨在调节相关途径的策略已成功应用于治疗各种疾病。事实上,最近通过高通量筛选 (HTS) 基于适当的细胞死亡测定法,已经鉴定出几种具有应用于癌症、缺血和神经退行性疾病的临床有希望的细胞毒性和细胞保护剂。鉴于不同的细胞死亡方式可能在不同的疾病中失调,越来越明显的是,这样的测定法不仅需要定量细胞死亡的程度,还需要能够区分各种途径。在这里,我们系统地描述了准确量化不同细胞死亡途径的方法,讨论了它们的优点和缺点,并重点介绍了那些适用于 HTS 的技术。

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