Fig. 6: MS1262 inhibition of G9a reversed AD proteopathology (AD-correlated proteome and phosphoproteome).
A Venn diagrams summarizing total number of proteins and phospho-sites identified in 5x-FAD and APP-NLGF mouse models in this study. Briefly, global/phospho-proteomic experiments were performed using proteins extracted from hippocampus of age matched wild-type controls (WT; n = 3), 5x-FAD/APPNLGF mice at mid/late-stage Alzheimer’s (AD; n = 4), and AD mice treated with MS1262 (AD-tr; n = 4). Samples were TMT-labeled and run in quadruplicate. B Bar charts summarizing number of proteins (global proteomics) and phospho-sites (phosphor-proteomics) showing statistically significantly (log2(FC) ± 0.2; p < 0.05; two-tailed unpaired Student’s t test) changes in comparison of AD vs WT and AD-MS1262 treated vs AD mice. C Heatmap summarizing pathway activity z-scores, calculated by Ingenuity Pathway Analysis (IPA) using differentially regulated proteins and phospho-sites shown in (B) for indicated comparisons (AD vs WT & AD-MS1262 treated vs AD) in 5x-FAD and APP-NLFG mice. MS1262 treatment reverses/ameliorates pathway activity changes seen in both mouse models of AD, when compared to age matched wild-type (WT) controls. D Heatmap summarizing MS1262-affected diseases and functions based on dysregulated proteins/phosphosites shown in (B). Z-scores were calculated using Ingenuity Pathway Analysis (IPA). E The network of indicated signaling pathways (see also Figures. S8-S9 & Data S1D–E).
