GSK3 Function in the Brain during Development, Neuronal Plasticity, and Neurodegeneration

Figure 4

Proposed model of GSK3 activation by amyloid-β protein in AD. Amyloid-β oligomers bind to the insulin receptor and inhibit PI3K/Akt pathway, and Akt is unable to phosphorylate and inactivate GSK3. Aβ also induces the expression of DKK1, which internalizes LRP6 receptor and inhibits Wnt signaling leading to GSK3 activation. Aβ can bind to Frizzled receptor (FzR) and inactivate Wnt signaling as well. ApoE also inhibits this signaling pathway and activates GSK3. Tau hyperphosphorylation and NFT formation may result from GSK3 overactivation.