In Vivo Screen for Neuroprotective Agents

项目总结/摘要 神经元凋亡已被证明参与了一些神经退行性疾病的发病机制 包括帕金森病（PD）、阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）和 中风目前，还没有简单的方法来评估体内神经元凋亡或神经保护， 脊椎动物此外，传统的脊椎动物测定法冗长且费力，是不切实际的 用于筛选化合物文库。一个有效的体内试验将是有用的预筛选候选药物 在进行昂贵的哺乳动物测试之前。这项研究的总体目标是开发一种快速， 定量体内斑马鱼测定以鉴定潜在的神经保护剂。第一阶段研究建立了一个 用于在脑中产生细胞凋亡的可重复模型和开发的筛选方法 体内神经保护剂。第二阶段的研究将使检测自动化，以增加筛选通量， 使用化合物库进行试点筛选，并确认化合物的神经保护作用 使用传统的哺乳动物模型。

Project Summary/Abstract Neuronal apoptosis has been shown to be involved in pathogenesis of several neurodegenerative disorders including Parkinson's Disease (PD), Alzheimer's Disease (AD), Amyotophic Lateral Sclerosis (ALS) and stroke. Currently, there is no simple method to assess neuronal apoptosis or neuroprotection in vivo in vertebrates. Furthermore, conventional vertebrate assays, which are lengthy and laborious, are impractical for screening compound libraries. A validated in vivo assay will be useful for prescreening drug candidates prior to performing expensive mammalian testing. The overall aim of this research is to develop a rapid, quantitative in vivo zebrafish assay to identify potential neuroprotectants. Phase I research established a reproducible model for generating apoptosis in the brain and developed methods for screening neuroprotectants in vivo. Phase II research will automate the assay to increase screening throughput, perform a pilot screen using a compound library and confirm neuroprotective effects of ¿hit¿ compounds using a conventional mammalian model.