Optimization of the African killifish platform for rapid drug screening for aggregate based neurodegenerative diseases

Abstract

There are currently no available drugs for neurodegenerative diseases, including Alzheimer’s disease.  We have developed the killifish as new vertebrate model system with high throughput capacity. The killifish is the shortest-lived vertebrate with a lifespan of ~4-6 months. In this rapid timeframe, the killifish exhibits multiple age-dependent phenotypes and pathologies that arise over decades in humans, including cognitive decline and neurodegeneration. We have also pioneered a genome-to-phenotype platform coupled with an automated feeding system, allowing for compound delivery in a manner compatible with lifespan and cognitive behavior studies. Leveraging the power of this vertebrate aging model, we have investigated age-dependent protein aggregation at a systems level and identified a set of aggregating proteins in the aging brain. There is huge potential to optimize the killifish platform for phenotypic screening of drug libraries, notably those targeted at protein aggregation, which is central to neurodegenerative diseases.