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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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

Fingerprint

Amyloid Precursor Protein Secretases
resveratrol
amyloid
Alzheimer disease
Amyloid
proteins
Alzheimer Disease
brain
disease models
Amyloid beta-Protein Precursor
leaves
grapes
cell culture
pathogenesis
Brain
peptides
drugs
Presenilin-1
stems
Lead compounds

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., ... 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

The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. / Hu, Jin; Lin, Ting; Gao, Yuehong; Xu, Junyue; Jiang, Chao; Wang, Guanghui; Bu, Guojun D; Xu, Huaxi; Chen, Haifeng; Zhang, Yun Wu.

In: PLoS One, Vol. 10, No. 1, e0115973, 28.01.2015.

Research output: Contribution to journalArticle

Hu, J, Lin, T, Gao, Y, Xu, J, Jiang, C, Wang, G, Bu, GD, Xu, H, Chen, H & Zhang, YW 2015, 'The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation', PLoS One, vol. 10, no. 1, e0115973. https://doi.org/10.1371/journal.pone.0115973
Hu, Jin ; Lin, Ting ; Gao, Yuehong ; Xu, Junyue ; Jiang, Chao ; Wang, Guanghui ; Bu, Guojun D ; Xu, Huaxi ; Chen, Haifeng ; Zhang, Yun Wu. / The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. In: PLoS One. 2015 ; Vol. 10, No. 1.
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