Fig. 2.

EE promotes the conversion of proNGF to mature NGF (mNGF) through increased plasmin levels. mNGF then binds to tyrosine kinase A (TrkA), which subsequently activates the PI3k-Akt and MAPK/ERK pathway and promotes neurogenesis, cell survival, cell proliferation and increased synaptic plasticity in the basal forebrain. As a result of this conversion, EE also indirectly decreases the activation of the JNK pathway signaling pathway by indirectly reducing proNGF levels (↓) and directly reducing p75^NTR levels (↓) in the brain. This results in lower JNK phosphorylation, consequently leading to decreased tau hyperphosphorylation, decreased APP phosphorylation and decreased cell death in the basal forebrain