期刊
PLOS ONE
卷 10, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0115973
关键词
-
资金
- National Natural Science Foundation of China [81202419, 81225008, 81161120496, 91332112, 91332114]
- Xiamen Science and Technology Key program grant [3502Z20100006]
- Fundamental Research Funds for the Central Universities of China
Accumulation and deposition of amyloid-beta peptide (A beta) in the brain is a primary cause of the pathogenesis of Alzheimer's disease (AD). Aa is generated from amyloid-beta precursor protein (APP) through sequential cleavages first by beta-secretase and then by.-secretase. Inhibiting a-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 Aa and sAPP beta 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据