In addition to reducing Tau phosphorylation, the neuroprotective actions of the inhibition of GSK3β also involve the regulation of β catenin. The levels of β catenin are regulated by oestradiol through the ERα–PI3K–AKT–GSK3β signalling pathway98,100. Studies in neuroblastoma cells have shown that the activation of the PI3K–AKT–GSK3β pathway induces the transloca¬tion of β catenin to the cell nucleus, which inhibits the transcriptional activity of ERα36 and regulates transcrip¬tional activity through T cell factor (TCF) and lymphoid enhancer-binding factor (LEF) proteins101 (FIG. 4). The set of genes regulated by oestradiol through this mechanism is similar but not identical to the set regulated by the canonical WNT signalling pathway101 (see below).