Figure 6.
S 24795 reduces Aβ42–α7nAChR association and removes Aβ42 from preformed Aβ42–Aβ42 and Aβ42–α7nAChR complexes by binding to Aβ15-20. Biotin-tagged α7nAChRs or Aβ42 peptides were trapped on streptavidin-coated 96-well plate by incubating with 2 nm α7nAChRs or Aβ42 at 25°C for 1 h. A, S 24795 added either simultaneously with or 10 min before 20 nm FITC-conjugated Aβ42 dose-dependently reduced FITC-conjugated Aβ42 interaction with biotinated α7nAChRs trapped on streptavidin-coated 96-well plate as measured by the residual FITC signals after washing. The data are expressed as mean ± SEM of percentage inhibition comparing S 24795- to vehicle-treated wells (n = 6–8). B, Aβ15-20 containing Aβ fragments (i.e., Aβ12-28, Aβ10-20, and Aβ15-20) reduced or prevented, whereas C terminus Aβ peptides (i.e., Aβ25-35, Aβ29-40, and Aβ37-43) enhanced S 24795-induced Aβ42 release from preformed Aβ42–α7nAChR complexes resulting from FITC-Aβ42 incubation with biotinated α7nAChRs trapped on streptavidin-coated 96-well plates. The data are mean ± SEM of percentage dissociation by S 24795, the indicated Aβ fragments alone or plus S 24795 (10 μm each) (n = 4–8). C, Aβ15-20-containing peptides (i.e., Aβ12-28, Aβ10-20, and Aβ15-20) blocked, whereas C terminus Aβ peptides (i.e., Aβ25-35, Aβ29-40, and Aβ37-43) increased S 24795-mediated release of Aβ42 from preformed Aβ42–Aβ42 complexes deriving from FITC-Aβ42 incubation with biotinated Aβ42 trapped on streptavidin-coated 96-well plates. The data expressed are mean ± SEM of percentage dissociation by S 24795, the indicated Aβ fragments alone or plus S 24795 (10 μm each) (n = 4–8). *p < 0.01, **p < 0.05 compared with vehicle control; #p < 0.01, ##p < 0.05 compared with 10 μm S 24795 alone.