Fig. 10

FRM-36143 reverses the effects of FAD presenilin mutants. a Total Aβ secreted by HEK cells expressing WT or mutant PS. Presenilin mutants cause a partial loss of function of γ-secretase leading to a decreased secretion of total Aβ peptides. b Presenilin mutations increase the Aβ₄₂:Aβ₄₀ ratio, which is reversed by FRM-36143. Presenilin mutations decrease the fourth cleavage cycle of γ-secretase as measured by the Aβ₃₈:Aβ₄₂ ratio (c) or the intracellular production of the peptides VVIA and VVIAT (d), both of which are reversed by FRM-36143. Data represent mean ± SEM of n = 4. Two-tailed unpaired t test: ** p < 0.001 and *** p < 0.0001: mutants vs. WT, ‡ p < 0.0001: FRM-36143 vs. DMSO, † p < 0.01: FRM-36143 vs. DMSO