Inhibition of canonical WNT signal¬ling by DKK1 results in the downregulation of BCL 2 and the upregulation of the pro apoptotic molecule BCL2 associated protein X (BAX) and the hyperphos-phorylation of Tau122. DKK1 expression is enhanced in neurodegenerative conditions, such as global cerebral ischaemia120,121. Experiments have shown that oestra¬diol prevents the upregulation of DKK1 under these conditions and that the inhibition of DKK1 expression by oestradiol promotes neuronal survival, reduces Tau hyperphosphorylation and reduces ischaemia-induced neuronal damage120,121. The inhibition of the expression of DKK1 by oestradiol is mediated by the attenuation of JNK–JUN signalling120, which is enhanced by global cerebral ischaemia120 and is downregulated by oestradiol through AKT123.