HDAC3 silencing promotes nonamyloidogenic APP processing and decreases Aβ1–42:Aβ1–40 ratio. HDAC3 silencing promotes nonamyloidogenic APP processing and.

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HDAC3 silencing promotes nonamyloidogenic APP processing and decreases Aβ1–42:Aβ1–40 ratio. HDAC3 silencing promotes nonamyloidogenic APP processing and decreases Aβ1–42:Aβ1–40 ratio. (A) 10 μM RGFP-966 increases expression of sAPPα and (B) cellular APP in HEK/APPsw. Immunoblots showing increase of (C) sAPPα and (D) cellular APP in response to 10 μM RGFP-966 in HEK/APPsw whole-cell extract. (E and F) 10 μM HDAC3 RGFP-966 decreased the expression of β-secretase components (BACE1 and BACE2). Lower concentrations of RGFP-966 did not influence BACE1 or BACE2 expression. (G) RGFP-966 decreased expression of secreted sAPPβ at 10 μM, while (H) decreasing neurotoxic secreted Aβ1–42 and increasing nontoxic secreted Aβ1–40 in a dose-dependent manner 48 h after treatment. Yellow indicates neuroprotective APP metabolites. Dark orange indicates APP metabolites and transcripts known to be pathogenic. One-way ANOVA with Dunnett’s multiple-comparisons test was used. The graphs represent mean ± SEM. **P < 0.01, ****P < 0.001; n = 4–7. Karolina J. Janczura et al. PNAS 2018;115:47:E11148-E11157 ©2018 by National Academy of Sciences