Insulin regulates Presenilin 1 localization via PI3K/Akt signaling

Abstract 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.