A Morphology- and Kinetics-Based Cascade for Human Neural Cell High Content Screening

Autor: Richards, Gillian R., Smith, Alison J., Parry, Frances, Platts, Amy, Chan, Grace K.Y., Leveridge, Mathew, Kerby, Julie E., Simpson, Peter B.
Zdroj: Assay and Drug Development Technologies; April 2006, Vol. 4 Issue: 2 p143-152, 10p
Abstrakt: The prospect of manipulating endogenous neural stem cells to replace damaged tissue and correct functional deficits represents a novel mechanism for treating a variety of central nervous system disorders. Using human neural precursor cultures and a variety of assays for studying stem cell behavior we have screened two libraries of commercially available compounds using an endpoint high content screening assay. We then performed detailed follow-up mechanistic studies on confirmed hits using endpoint and kinetics assays to characterize and differentiate the mechanisms of action of these compounds. The screening cascade employed successfully identified a number of active compounds with differing mechanisms of action. This approach shows how hits from a phenotypic screen can be prioritized and characterized by high content screening to identify potentially novel mechanisms and druggable targets to take forward into more conventional highthroughput screeening approaches.
Databáze: Supplemental Index