Carbon monoxide attenuates amyloidogenesis via down-regulation of NF-κB-mediated BACE1 gene expression.

ABSTRACT: Amyloid-β (Aβ) peptides, the major constituent of plaques, are generated by sequential proteolytic cleavage of the amyloid precursor protein (APP) via β-secretase (BACE1) and the γ-secretase complex. It has been proposed that the abnormal secretion and accumulation of Aβ are the initial causative events in the development of Alzheimer's disease (AD). Drugs modulating this pathway could be used for AD treatment. Previous studies indicated that carbon monoxide (CO), a product of heme oxygenase (HO)-1, protects against Aβ-induced toxicity and promotes neuroprotection. However, the mechanism underlying the mitigative effect of CO on Aβ levels and BACE1 expression is unclear. Here, we show that CO modulates cleavage of APP and Aβ production by decreasing BACE1 expression in vivo and in vitro. C

SUBMITTER: Kim HJ 

PROVIDER: S-EPMC6351829 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature