title: 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, 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.
authors.affiliation: School of Human Health Sciences, Kyoto University Graduate School of Medicine, 53, Shogoinkawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Maesako
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kubota
authors.forename: Koichi
authors.initials: K
authors.lastname: Ando
authors.forename: Akira
authors.initials: A
authors.lastname: Kuzuya
authors.forename: Megumi
authors.initials: M
authors.lastname: Asada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kihara
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
mesh_terms: 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
chemical_list: 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