Figure 1

GSK3/p53 hypothesis for AD. A Under normal conditions p53 is bound to Mdm2 which ubiquitinates and targets p53 for proteasomal degradation. B Under conditions of stress, p53 is stabilised and it can form complex with GSK3β. This results in increased activity of GSK3β which leads to hyperphosphorylation of tau and increased production of Aβ. Aβ affects p53 pools by increasing its transcription rate and through inhibition of the proteasome. Note that we also assume that GSK3β can also bind to phosphorylated p53.