| Abstract |
In an attempt to screen efficient compounds for treatment of Alzheimer's disease, we develop a cell-based assay system with multiple readout. Two fluorescent reporter systems, specific for beta-secretase and gamma-secretase, respectively, were developed and evaluated. The beta-secreatase-specific reporter was weak or no fluorescent signal in a human cell line. After treatment of inhibitor for beta-secretase, strong granule-like fluorescent signal was observed. The gamma-secretase-specific reporter exhibitedstrong fluorescent signal in nucleus of cells without specific inhibitor. With treatment of specific inhibitor, the reporter did not enter into cell nucleus and distributed to cytoplasm. With different fluorescent signal such as green and red, two reporter systems were combined in a single assay. As a result, this multiplex assay system can discriminate the specificity of inhibitors against Ab processing.
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