Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Sun, Miaoa; 1 | Zhou, Tinga | Zhou, Lianga; 1 | Chen, Qiangb; * | Yu, Yana | Yang, Huana | Zhong, Kaiyina | Zhang, Ximenga | Xu, Fengc | Cai, Shaoqingc | Yu, Alberta | Zhang, Huid | Xiao, Ruizhongd | Xiao, Dongshengd | Chui, Dehuaa; d; *
Affiliations: [a] Neuroscience Research Institute and Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China | [b] Department of Neurology, Ningbo Beilun Hospitals, Ningbo, China | [c] Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing, China | [d] Department of Neurology, Peking University Third Hospital, Beijing, China
Correspondence: [*] Correspondence to: Dr. Dehua Chui, Neuroscience Research Institute, Peking University Health Science Center, 38 Xueyuan Road, Hai Dian District, 100191, Beijing, China. E-mail: [email protected] and Dr. Qiang Chen, Department of Neurology, Ningbo Beilun Hospitals, Ningbo 315806, China. E-mail: [email protected].
Note: [1] These authors contributed equally to this paper.
Abstract: Formononetin, an active constituent of the Chinese herb Astragali Radix, has been reported to have beneficial effects for Alzheimer's disease (AD). Yet the mechanism of this effect remains to be elucidated. The present study shows that formononetin increases soluble-AβPPα (sAβPPα) secretion and thus protects human-AβPP Swedish mutation cell (N2a-AβPP cell) from hypoxia-induced apoptosis. Using hypoxic N2a-AβPP cell as an in vitro model of AD-like pathology, we confirmed that regular treatment with formononetin could have neuroprotective effects, followed respectively by reduced caspase 3 activity and increased cell viability. Strikingly, our data revealed that the caspase 3-blocking effect of formononetin was largely mediated by stimulation of α-secretase cleavage of AβPP, and increasing the secretion of its soluble form, sAβPPα. Moreover, the protective effect of formononetin was totally inhibited by TAPI-2, an α-secretase complex inhibitor, suggesting the role of the sAβPPα pathway in the neuroprotective response to formononetin. We also found that the stimulative effect of formononetin on α-secretase activity was mainly conducted by upregulating ADAM10 expression at the transcriptional level. Altogether, our study provides novel insights into how formononetin mediates stimulation of the ADAM10-sAβPPα pathway and exerts a neuronal protective effect.
Keywords: ADAM10, amyloid-β protein precursor (AβPP), formononetin, soluble-AβPPα
DOI: 10.3233/JAD-2011-110506
Journal: Journal of Alzheimer's Disease, vol. 28, no. 4, pp. 795-808, 2012
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
[email protected]
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office [email protected]
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
如果您在出版方面需要帮助或有任何建, 件至: [email protected]