Extended Data Fig. 8: Investigation on the specificity of mHTT-lowering effects of mHTT–LC3 linker compounds.
From: Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds
a, Representative western blots and quantifications of cultured cortical neurons treated with the indicated compounds. None of the proteins tested showed a clear effect (>10%). b, Volcano plots of the proteomics analysis of cortices from intraperitoneally injected HD mice (10 month old, 4 mice per group, injected for 14 days). Mice were injected with 0.5 mg kg−1 protein with 110 μg kg−1 DMSO, and equal amount of vehicle containing DMSO was injected in the control mice. Only proteins detected in both groups of samples used for comparisons were calculated and plotted. Red arrows indicate HTT. See Supplementary Table 2 for complete datasets. The bar plots indicate the total HTT levels normalized to the DMSO control. The actual mHTT reduction is anticipated to be higher, because the compounds reduced mHTT in an allele-selective manner. c, Similar to b, but in cultured cortical neurons (from postnatal day 0 pups, three wells per group). See Supplementary Table 3 for complete datasets. In all panels, data are mean ± s.e.m.
