Estrogen stimulates degradation of beta-amyloid peptide by up-regulating neprilysin.

ABSTRACT: Postmenopausal estrogen depletion is a characterized risk factor for Alzheimer disease (AD), a human disorder linked to high levels of beta-amyloid peptide (Abeta) in brain tissue. Previous studies suggest that estrogen negatively regulates the level of Abeta in the brain, but the molecular mechanism is unknown. Here, we provide evidence that estrogen promotes Abeta degradation mainly through a principal Abeta degrading enzyme, neprilysin, in neuroblastoma SH-SY5Y cells. We also demonstrate that up-regulation of neprilysin by estrogen is dependent on both estrogen receptor alpha and beta (ERalpha and ERbeta), and ligand-activated ER regulates expression of neprilysin through physical interactions between ER and estrogen response elements (EREs) identified in the neprilysin gene. These resu

SUBMITTER: Liang K 

PROVIDER: S-EPMC2801294 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature