a INRS-Institut Armand-Frappier , Laval , Canada.
b Department of Neuroscience , FRQS Groupe de recherche sur le système nerveux central and CRCHUM, University of Montréal , Montréal , Canada.
Expert Opin Drug Discov. 2016 Aug;11(8):797-804. doi: 10.1080/17460441.2016.1196183. Epub 2016 Jun 13.
Simple animal models have enabled great progress in uncovering the disease mechanisms of amyotrophic lateral sclerosis (ALS) and are helping in the selection of therapeutic compounds through chemical genetic approaches.
Within this article, the authors provide a concise overview of simple model organisms, C. elegans, Drosophila and zebrafish, which have been employed to study ALS and discuss their value to ALS drug discovery. In particular, the authors focus on innovative chemical screens that have established simple organisms as important models for ALS drug discovery.
There are several advantages of using simple animal model organisms to accelerate drug discovery for ALS. It is the authors' particular belief that the amenability of simple animal models to various genetic manipulations, the availability of a wide range of transgenic strains for labelling motoneurons and other cell types, combined with live imaging and chemical screens should allow for new detailed studies elucidating early pathological processes in ALS and subsequent drug and target discovery.
简单的动物模型在揭示肌萎缩侧索硬化症 (ALS) 的疾病机制方面取得了巨大进展,并通过化学遗传学方法帮助选择治疗化合物。
本文作者简要概述了已被用于研究 ALS 的简单模式生物,秀丽隐杆线虫、果蝇和斑马鱼,并讨论了它们对 ALS 药物发现的价值。特别是,作者重点介绍了创新性的化学筛选,这些筛选已将简单的生物体确立为 ALS 药物发现的重要模型。
使用简单的动物模型生物来加速 ALS 药物发现有几个优势。作者特别相信,简单动物模型对各种遗传操作的适用性、广泛的用于标记运动神经元和其他细胞类型的转基因品系的可用性,以及与活体成像和化学筛选相结合,应该可以进行新的详细研究,阐明 ALS 中的早期病理过程以及随后的药物和靶标发现。