Figure 6
From: A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models
MK-28 improves systemic function and survival in R6/2 mice and induces increased levels of eIF2α-P in the mouse brain striatum. (A) Blood glucose analysis during the symptomatic phases show elevated glucose levels when compared with the asymptomatic phase for TG animals (n = 6 TG, 8 TG + MK28, 10 WT). The bars in the graph indicate medians and interquartile range. Significance * p = 0.028 Anova Newman-Keuls post hoc. (B) MK-28 reduced the relative increase of blood glucose between the asymptomatic and symptomatic phases. Medians and interquartile range; significance **p = 0.0045 by Two-tailed Ttest. (C) Survival of R6/2 mice is significantly increased upon treatment with MK-28. TG mice receiving MK-28 (blue) or vehicle (red) were analysed (n = 13/group), showing a significant increase in the survival of MK-28 treated mice (median survival 97 and 89 days, respectively, p = 0.0469). Ratio 1.887, 95% CI of ratio 0.7726 to 4.611 (Gehan-Breslow-Wilcoxon test for comparisons of Kaplan-Meier survival curves). (D) Analysis of the striatum in mice brain slices by immunofluorescence. eIF2α-P levels (red: total eIF2α, green: eIF2α-P) were slightly increased in the brain of the TG animals when compared to the WT at baseline, and they were significantly increased upon treatment with MK-28 in both TG and WT mice. Bar = 20 μm. The bars in the graph indicate medians and interquartile range. Significance **p (eIF2α-P WT vs. WT + MK-28) 0.003, p (eIF2α-P HD vs. HD + MK-28) 0.007, Two-tailed Ttest.
