Figure 7.

Multiple structurally diverse γ-secretase inhibitors regulate processing by α- and β-secretase. (A) γ-30 cells were treated with various γ inhibitors for APP, and the CM and lysates were analyzed for the indicated proteins. (B) Western blot quantification of APPs-α was performed on CM samples from A, normalized to total APP levels in the lysate, and then normalized to DMSO-treated control samples. A one-way ANOVA with Dunnett’s posttest using DMSO as the control was performed. n = 6. (C) APPs-β ELISA was performed and quantified. All samples were equalized for APP levels, normalized to the DMSO-alone sample, and then analyzed by the same statistical test as in B. n = 4. (D) Levels of APP CTFs in lysates were plotted against APPs-α levels in CM (from Fig. 8 A) and fitted with a linear regression line. n = 36 from two independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

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