SiRNA knockdowns of influential aggregate hubs reduce aggregation in human cells. (a) Fluorescence images of thioflavin T-stained SH-SY5Y-APPSw cells after liposomal transfection with siRNA constructs targeting 14-3-3 paralogs or their interacting partners. (b) Histogram of means ± SEM for Thioflavin T staining of amyloid as in (a). (c) Intensity of SYPRO-Ruby-stained gel lanes for sarkosyl-insoluble aggregates isolated from SY5Y-APPSw cells exposed to RNAi constructs; (d) western blot probed with antibody to GRP78, 14-3-3, or GAPDH; gels were loaded with total protein extracted from SH-SY5Y-APPSw cells treated with RNAi constructs indicated; (e) mean ± SEM of band intensity for 14-3-3 or GRP78, each normalized to GAPDH. (b,c,e) Significance based on two-tailed t-tests: * p < 0.05; ** p < 0.005; *** p < 10−7; **** p < 10−17. For each assay, 100 < N < 150.