Insulin regulates Presenilin 1 localization via PI3K/Akt signaling

Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies [13,22,23], the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid β (Aβ) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/β-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/β-catenin complex regulates Aβ production [28], it is likely that insulin signaling affects Aβ pathology by regulating PS1 localization.