Figure 2.

LX2343 reduced Aβ production involving both JNK/APP^Thr668 pathway regulation and BACE1 enzymatic inhibition. Western blotting and its quantification results demonstrated that LX2343 reduced the phosphorylation of JNK and APP^Thr668, decreased the protein level of sAPPβ, and had no effects on the protein level of BACE1 in HEK293-APP_sw (A, B) and CHO-APP (C, D) cells (one-way ANOVA, Dunnett's multiple comparison test. n=3. ^*P<0.05, ^**P<0.01 vs STZ). ELISA results indicated that LX2343 decreased sAPPβ in HEK293-APPsw and CHO-APP cells (E, F) (one-way ANOVA, Dunnett's multiple comparison test. n=3. ^*P<0.05, ^**P<0.01 versus STZ). LX2343 inhibited BACE1 activity with an IC₅₀ of 11.43±0.36 μmol/L in vitro, and LX2343 concentration is expressed on a log₁₀ scale (G, H) (TDC²⁸: 2,2′,4′-trihydroxychalcone, BACE1 non-competitive inhibitor. One-way ANOVA, Dunnett's multiple comparison test. ^**P<0.01 vs DMSO; TDC, t test. n=3. GAPDH was used as loading control in the Western blot assays. All data were obtained from three independent experiments and are presented as the mean±SEM.