High Throughput Screening for Neurodegeneration and Complex Disease Phenotypes
Hemant Varma, Donald C. Lo and Brent R. Stockwell
Affiliation: Department of Biological Sciences, Columbia University, 614 Fairchild Center MC2406, 1212 Amsterdam Avenue, New York, NY 10027, USA.
Keywords: High throughput, screening, Huntington's disease, drugs, neurodegeneration, high-content, aggregation, cell death
High throughput screening (HTS) for complex diseases is challenging. This stems from the fact that complex phenotypes are difficult to adapt to rapid, high throughput assays. We describe the recent development of high throughput and high-content screens (HCS) for neurodegenerative diseases, with a focus on inherited neurodegenerative disorders, such as Huntingtons disease. We describe, among others, HTS assays based on protein aggregation, neuronal death, caspase activation and mutant protein clearance. Furthermore, we describe high-content screens that are being used to prioritize hits identified in such HTS assays. These assays and screening approaches should accelerate drug discovery for neurodegenerative disorders and guide the development of screening approaches for other complex disease phenotypes.
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