In Vivo Screen for Neuroprotective Agents

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DESCRIPTION (provided by applicant): 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. By providing a rapid in vivo assay for prescreening drug candidates prior to performing expensive mammalian testing, the proposed zebrafish assay will facilitate drug development for neurodegenerative disorders and stroke.