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

Jin Hu, Ting Lin, Yuehong Gao, Junyue Xu, Chao Jiang, Guanghui Wang, Guojun D Bu, Huaxi Xu, Haifeng Chen, Yun Wu Zhang

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18 Scopus citations

Abstract

Accumulation and deposition of amyloid-β peptide (Aβ) in the brain is a primary cause of the pathogenesis of Alzheimer's disease (AD). Aβ is generated from amyloid-β precursor protein (APP) through sequential cleavages first by β-secretase and then by γ-secretase. Inhibiting β-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 Aβ and sAPPβ 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 α-secretases ADAM10 and TACE, and the γ-secretase component Presenilin 1, nor γ-secretase-mediated Notch processing and TACE activity. In contrast, although miyabenol C has no effect on altering protein levels of the β-secretase BACE1, it can inhibit both in vitro and in vivo β-secretase activity. Together, our results indicate that miyabenol C is a prominent β-secretase inhibitor and lead compound for AD drug development.

Original languageEnglish (US)
Article numbere0115973
JournalPLoS One
Volume10
Issue number1
DOIs
StatePublished - Jan 28 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hu, J., Lin, T., Gao, Y., Xu, J., Jiang, C., Wang, G., Bu, G. D., Xu, H., Chen, H., & Zhang, Y. W. (2015). The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. PLoS One, 10(1), [e0115973]. https://doi.org/10.1371/journal.pone.0115973