Fig. 2.
Hit compounds from the yeast screen inhibit polyQ aggregation in mammalian cells. (A) Structures of four hits from the yeast primary screen (C1-C4) that inhibit polyQ aggregation in PC12 cells. (B) Fluorescence microscopic assessment of Htt-103Q-EGFP aggregation in control- or compound-treated PC12 cells. Cells were treated with DMSO (control, Top), 2.5 μM C4 (Middle), or 10 μM Congo red (a known aggregation inhibitor, Bottom). Aggregates are indicated by arrows. (C and D) Inhibition of HD 51Q aggregation in Cos1 cells by compounds C1, C3, and C4, assessed using the filter-trap assay. (C) Immunodetection of insoluble (aggregated) HD 51Q trapped on the filter. (D) Quantification of results shown in C. Signal intensity from the sample incubated in the presence of the solvent alone was used as reference and set at 100%.