Figure 6.

Upregulation of CLEAR genes and clearance of HTT aggregates. (A) Expression of eight CLEAR genes, CSTD, LAMP1, HEXA, CLCN7, ATP6V0A1 (ATP-A1), SQSTM1, UVRAG and GABARAP was assessed after treatment with 1 µM compound for 48 h and showed significant increase of multiple genes with NK176 and NK177 treatment. (B) GFP-Ex1HTT74Q HTT expression can be induced, and visualized as bright puncta where aggregates are formed. Nuclei stained with Hoechst 33,342. (C) Total-GFP fluorescence shows reduction in signal after treatment with either NK176 or NK177 at 1 and 2 µM (n = 3). (D) The percentage of cells bearing aggregates is reduced at higher concentrations, but the difference is non-significant due to the variability in the assay output. n = 3 except for NK176 and NK177 1 and 2 µM where n = 2. * p < 0.05, *** p < 0.0, **** p < 0.0001 Two-Way ANOVA with Dunnett’s multiple comparisons test.