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 I (PSI), a key molecule of amylold beta (A beta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PSI phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates A beta production [28], it is likely that insulin signaling affects Ail pathology by regulating PSI localization (C) 2010 Elsevier Ireland Ltd All rights reserved