Figure 7.
Effect of cdk5 inhibitor CP-681301 on GSK3β regulation and tau phosphorylation in neonatal p25 mice. A, Representative blots showing the effect of CP-681301 on GSK3β, GSK3β–S9, and tau phosphorylated at sites pS199 and pS235, relative to total tau, and dephosphorylated tau (Tau1) in neonatal Ntg mice treated with vehicle (Ntg/Veh; n = 7), p25 mice treated with vehicle (p25/Veh; n = 7), and p25 mice treated with CP-681301 (p25/CP; n = 6). Actin was used as a loading control for this study. B, Statistical analysis of GSK3β–S9 phosphorylation, pS199, and total dephosphorylated tau (Tau1) in Ntg mice treated with vehicle (Ntg/Veh), p25 mice treated with vehicle (p25/Veh), and p25 mice treated with cdk5 inhibitor CP-681301 (p25/CP). The cdk5 inhibitor reversed the effects of overactive cdk5 in the p25 mice, leading to reduced inhibitory phosphorylation of GSK3β and increased phosphorylation of tau at relevant sites.