Figure 3.

Pin1 in the metabolic pathway acts as a negative regulator of AMPK and modulates the Akt active form. Insulin promotes neuronal cytoskeletal dynamics via Akt phosphorylation. Activation of insulin signaling leads usually to activation of phosphatidyl-inositol-3-kinase/Akt (PI3K/Akt) pathway. After being activated through its phosphorylation mainly at Thr308 residue, Akt phosphorylates glycogen synthase kinase-3β (GSK-3β) at Ser9 and inactivates GSK-3β kinase activity. GSK-3β is also the major protein kinase regulating tau phosphorylation in the brain. Pin1 modulates all these players involved in the signaling cascade.