Health Topics A-Z | Estrogen Stimulates Degradation of {beta}-Amyloid Peptide by Up-regulating Neprilysin [Transcription, Chromatin, and Epigenetics]

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Estrogen Stimulates Degradation of {beta}-Amyloid Peptide by Up-regulating Neprilysin [Transcription, Chromatin, and Epigenetics]

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