Fig. 3: The positive effects of neflamapimod on pathology and function in Ts2 mice appear to be mediated by inhibition of the p38α kinase pathway and related to BACE1 and βCTF reductions. | Nature Communications

Fig. 3: The positive effects of neflamapimod on pathology and function in Ts2 mice appear to be mediated by inhibition of the p38α kinase pathway and related to BACE1 and βCTF reductions.

From: Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration

Fig. 3

a Western blot analysis of p38α, phosphorylated-p38 (p-p38), and downstream substrates MK2 and MNK1 in tissue homogenates of the brain cortex after 2 weeks of either vehicle or NFMD treatment (n = 5 for Ts2-NFMD, and n = 6 for other treatment groups). b Quantification of the western blot images shown with Image J and graphed with GraphPad Prism 8.0.1 [Ordinary One-Way ANOVA, For p-p38 F(3, 19) = 6.658, R square = 0.540, for 2 N vs Ts2, p = 0.0044, 95% CI = −0.760, −0.131; for 2 N vs Ts2-NFMD p = 0.0495, 95% CI = −0.656 −0.000194; For MK2 F(3, 19) = 10.33, R square = 0.610, for 2 N vs Ts2-NFMD, p = 0.0005, 95% CI = 0.182, 0.541; for Ts2 vs Ts2-NFMD p = 0.0166, 95% CI = 0.0457, 0.404; For pMK2 F(3, 19) = 2.850, R square = 0.310, for 2 N vs Ts2, p = 0.0178, 95% CI = −1.095, −0.117; for 2 N vs 2N-NFMD p = 0.0469, 95% CI = −0.985, −0.0076; for Ts2 vs Ts2-NFMD p = 0.0166, 95% CI = 0.0457, 0.404; For MNK1 F(3, 19) = 15.11, R square = 0.705, for 2 N vs Ts2, p = 0.0003, 95% CI = 0.235, 0.668; for 2 N vs 2N-NFMD p = 0.023, 95% CI = 0.0393, 0.472, for Ts2 vs Ts2-NFMD, p = 0.0347, 95% CI = 0.0197, 0.473; For pMNK1 F(3, 19) = 6.285, R square = 0.498, for 2 N vs Ts2-k NFMD, p = 0.0063, 95% CI = 0.156, 0.824; for TS2 vs Ts2-NFMD p = 0.0428, 95% CI = 0.125, 0.681]. c, d Subsequent western blot analysis for full length APP (APPfl), APP-βCTF and BACE1 and western blot image quantified with Image J and graphed with GraphPad Prism 8.0.1 (Ordinary One-Way ANOVA, For APPfl F(3, 19) = 23.33, R square = 0.786, for 2 N vs Ts2, p < 0.0001, 95% CI = −684, −0.376; for 2 N vs Ts2-NFMD p = 0.0001, 95% CI = −0.532, −0.209; For APP-βCTF F(3, 19) = 8.167, R square = 0.563, for 2 N vs Ts2, p = 0.0003, 95% CI = −1.027, −0.367; for Ts2 vs Ts2-NFMD p = 0.0007, 95% CI = 0.3187, 1.010; For BACE1 F(3, 19) = 12.86, R square = 0.670, for 2 N vs Ts2-NFMD, p = 0.0001, 95% CI = 0.158, 0.491; for Ts2 vs TS2-NFMD p = 0.0469, 95% CI = −0.00185, 0.335). Data are presented as mean values ± SEM. Statistical significance is represented by asterisks *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. Source data are provided as a Source Data File.

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