Research Paper Volume 14, Issue 20 pp 8221—8242

Figure 13. GRP78 plays a key role in regulating the expression of APP and Tau after exposure of neuronal cells and microglia to AR12 and neratinib. HCN2 and BV2 cells were transfected with a scrambled siRNA or with siRNA molecules to knock down the expression of GRP78, HSP70 or HSP90 and in parallel co-transfected to express Tau or APP. After 24h, cells were treated with vehicle control, AR12 (2 μM), neratinib (50 nM) or the drugs in combination for 6h. Cells were fixed in place and immunostaining performed to determine the expression of APP, Tau and ERK2. (n = 3 +/-SD) * p < 0.05 less than vehicle control; ** p < 0.05 less than AR12 value; ¶ p < 0.05 less than corresponding value in siSCR cells. In parallel, HCN2 and BV2 cells were transfected with an empty vector plasmid CMV or with plasmids to express GRP78, HSP70 or HSP90 and in parallel co-transfected to express Tau or APP. After 24h, cells were treated with vehicle control, AR12 (2 μM), neratinib (50 nM) or the drugs in combination for 6h. Cells were fixed in place and immunostaining performed to determine the expression of APP, Tau and ERK2. (n = 3 +/-SD) * p < 0.05 less than vehicle control; ** p < 0.05 less than AR12 value; † p < 0.05 greater than corresponding value in siSCR cells.