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, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) 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/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization.
Maesako
Masato
M
School of Human Health Sciences, Kyoto University Graduate School of Medicine, 53, Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Uemura
Kengo
K
Kubota
Masakazu
M
Ando
Koichi
K
Kuzuya
Akira
A
Asada
Megumi
M
Kihara
Takeshi
T
Kinoshita
Ayae
A
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D053764:Presenilin-1 / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection / Q000379:methods
D015820:Cadherins; D004791:Enzyme Inhibitors; D007328:Insulin; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012694:Serine; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt