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利用斑马鱼模型助力药物发现与靶点验证。

The Use of the Zebrafish Model to Aid in Drug Discovery and Target Validation.

作者信息

Yoganantharjah Prusothman, Gibert Yann

机构信息

Metabolic Research Unit, Metabolic Genetic Diseases Laboratory, Deakin University School of Medicine, 75 Pigdons Road, Geelong VIC 3216. Australia.

出版信息

Curr Top Med Chem. 2017;17(18):2041-2055. doi: 10.2174/1568026617666170130112109.

Abstract

The zebrafish is fast becoming a leading and prominent model organism used by researchers for developmental biology, and research in modeling human diseases in zebrafish is being undertaken at a fast pace. Many therapeutic areas, including oncology and cardiovascular diseases to name a few all have zebrafish models based on known disease mechanisms that are translatable to modes of action in humans. Many novel assays have been and are continuing to be developed to study human disease in zebrafish. Prominent methods to identify novel drug targets within the organism include, chemical mutagenesis, insertional mutagenesis and high throughput small molecule screens. Methods to validate potential drug targets include reverse and forward genetics, transgenesis and gene knockout. This review summarizes the important contributions made using the zebrafish model in recent years to aid in drug discovery and target validations in the highly important medical field of cancer medicine, cardiovascular disease and the emerging role of the zebrafish model as a platform for toxicity screening.

摘要

斑马鱼正迅速成为研究人员用于发育生物学的主要且重要的模式生物,并且利用斑马鱼对人类疾病进行建模的研究正在快速推进。许多治疗领域,包括肿瘤学和心血管疾病等,都有基于已知疾病机制的斑马鱼模型,这些模型可转化为人类的作用方式。已经并正在继续开发许多新颖的检测方法来研究斑马鱼中的人类疾病。在该生物体中鉴定新型药物靶点的突出方法包括化学诱变、插入诱变和高通量小分子筛选。验证潜在药物靶点的方法包括反向和正向遗传学、转基因和基因敲除。本综述总结了近年来使用斑马鱼模型在癌症医学、心血管疾病等极为重要的医学领域中对药物发现和靶点验证所做出的重要贡献,以及斑马鱼模型作为毒性筛选平台的新兴作用。

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