The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation

16Citations
Citations of this article
24Readers
Mendeley users who have this article in their library.

Abstract

Accumulation and deposition of amyloid-beta peptide (Abeta) in the brain is a primary cause of the pathogenesis of Alzheimer's disease (AD). Abeta is generated from amyloid-beta precursor protein (APP) through sequential cleavages first by beta-secretase and then by gamma-secretase. Inhibiting beta-secretase activity is believed to be one of the most promising strategies for AD treatment. In the present study, we found that a resveratrol trimer, miyabenol C, isolated from stems and leaves of the small-leaf grape (Vitisthunbergii var. taiwaniana), can markedly reduce Abeta and sAPPbeta levels in both cell cultures and the brain of AD model mice. Mechanistic studies revealed that miyabenol C affects neither protein levels of APP, the two major alpha-secretases ADAM10 and TACE, and the gamma-secretase component Presenilin 1, nor gamma-secretase-mediated Notch processing and TACE activity. In contrast, although miyabenol C has no effect on altering protein levels of the beta-secretase BACE1, it can inhibit both in vitro and in vivo beta-secretase activity. Together, our results indicate that miyabenol C is a prominent beta-secretase inhibitor and lead compound for AD drug development.

Cite

CITATION STYLE

APA

Hu, J., Lin, T., Gao, Y., Xu, J., Jiang, C., Wang, G., … Zhang, Y. W. (2015). The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. PLoS ONE, 10(1). https://doi.org/10.1371/journal.pone.0115973

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free