The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation.
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 activit...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115973&type=printable |
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| author | Jin Hu Ting Lin Yuehong Gao Junyue Xu Chao Jiang Guanghui Wang Guojun Bu Huaxi Xu Haifeng Chen Yun-wu Zhang |
| author_facet | Jin Hu Ting Lin Yuehong Gao Junyue Xu Chao Jiang Guanghui Wang Guojun Bu Huaxi Xu Haifeng Chen Yun-wu Zhang |
| author_sort | Jin Hu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-38190cb5ecdc412c90c372e55a698ce5 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-38190cb5ecdc412c90c372e55a698ce52025-08-20T02:15:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01101e011597310.1371/journal.pone.0115973The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation.Jin HuTing LinYuehong GaoJunyue XuChao JiangGuanghui WangGuojun BuHuaxi XuHaifeng ChenYun-wu ZhangAccumulation 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115973&type=printable |
| spellingShingle | Jin Hu Ting Lin Yuehong Gao Junyue Xu Chao Jiang Guanghui Wang Guojun Bu Huaxi Xu Haifeng Chen Yun-wu Zhang The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. PLoS ONE |
| title | The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. |
| title_full | The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. |
| title_fullStr | The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. |
| title_full_unstemmed | The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. |
| title_short | The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation. |
| title_sort | resveratrol trimer miyabenol c inhibits β secretase activity and β amyloid generation |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115973&type=printable |
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