Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits.

ABSTRACT: Extensive evidence has indicated that a high rate of cholesterol biogenesis and abnormal neuronal energy metabolism play key roles in Alzheimer's disease (AD) pathogenesis. Here, for we believe the first time, we used osmotin, a plant protein homolog of mammalian adiponectin, to determine its therapeutic efficacy in different AD models. Our results reveal that osmotin treatment modulated adiponectin receptor 1 (AdipoR1), significantly induced AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) activation and reduced SREBP2 (sterol regulatory element-binding protein 2) expression in both in vitro and in vivo AD models and in Adipo^-/- mice. Via the AdipoR1/AMPK/SIRT1/SREBP2 signaling pathway, osmotin significantly diminished amyloidogenic Aβ production, abundance and aggregation

SUBMITTER: Shah SA 

PROVIDER: S-EPMC5322276 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature