Figure 3
From: Reduction of β-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease
A) Effect of celastrol on Aβ production in 7 W CHO cells overexpressing wild-type human APP. Human Aβ was measured by ELISAs in the culture media surrounding the cells following 24 hours of treatment with different doses of celastrol. Dose response curves for both Aβ1-40 and Aβ1-42 were established revealing an IC50 of approximately 900 nM for celastrol. ANOVA reveals a significant main effect of celastrol on Aβ 1-40 (P < 0.001) and Aβ 1-42 production (P < 0.015). Post-hoc comparisons show statistically significant effects of celastrol at 1000 nM, 25000 nM and 5000 nM for both Aβ 1-40 and Aβ 1-42 (P < 0.001). B) Effect of celastrol on APP processing and NFκB in CHO cells overexpressing wild-type human APP. Celastrol dose dependently inhibited APPsβ secretion, APP-CTFβ level as well as NFκB p65 and IKBα phosphorylation. C) Histogram representing the quantification of APPsβ/APPsα, APP-CTFβ/actin as well as phospho-NFκB p65/actin and phospho-IKBα/actin chemoluminescent signals. ANOVA reveals a significant main effect of celastrol on APPsβ secretion, APP-CTFβ level, phospho-NFκB p65 and phospho-IKBα levels (P < 0.001). Post-hoc comparisons show a statistical significance for celastrol at 2 and 5 μM for all the parameters studied (P < 0.05) showing that celastrol dose dependently inhibits the β-cleavage of APP while suppressing NFκB activity. (* P < 0.05; ** P < 0.001).