Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease

Jo, Dong-Gyu, Arumugam, Thiruma V., Woo, Ha-Na, Park, Jong-Sung, Tang, Sung-Chun, Mughal, Mohamed, Hyun, Dong-Hoon, Park, Jun-Hyung, Choi, Yun-Hyung, Gwon, A-Ryeong, Camandola, Simonetta, Cheng, Aiwu, Cai, Huaibin, Song, Weihong, Markesbery, William R. and Mattson, Mark P. (2010) Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease. Neurobiology of Aging, 31 6: 917-925. doi:10.1016/j.neurobiolaging.2008.07.003

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Author Jo, Dong-Gyu
Arumugam, Thiruma V.
Woo, Ha-Na
Park, Jong-Sung
Tang, Sung-Chun
Mughal, Mohamed
Hyun, Dong-Hoon
Park, Jun-Hyung
Choi, Yun-Hyung
Gwon, A-Ryeong
Camandola, Simonetta
Cheng, Aiwu
Cai, Huaibin
Song, Weihong
Markesbery, William R.
Mattson, Mark P.
Title Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease
Formatted title
Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease
Journal name Neurobiology of Aging   Check publisher's open access policy
ISSN 0197-4580
1558-1497
Publication date 2010-06
Year available 2008
Sub-type Article (original research)
DOI 10.1016/j.neurobiolaging.2008.07.003
Volume 31
Issue 6
Start page 917
End page 925
Total pages 9
Editor Paul D. Coleman
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2011
Language eng
Formatted abstract
β-Secretase (BACE1), an enzyme responsible for the production of amyloid β-peptide (Aβ), is increased by oxidative stress and is elevated in the brains of patients with sporadic Alzheimer's disease (AD). Here, we show that oxidative stress fails to induce BACE1 expression in presenilin-1 (γ-secretase)-deficient cells and in normal cells treated with γ-secretase inhibitors. Oxidative stress-induced β-secretase activity and sAPPβ levels were suppressed by γ-secretase inhibitors. Levels of γ- and β-secretase activities were greater in brain tissue samples from AD patients compared to non-demented control subjects, and the elevated BACE1 level in the brains of 3xTgAD mice was reduced by treatment with a γ-secretase inhibitor. Our findings suggest that γ-secretase mediates oxidative stress-induced expression of BACE1 resulting in excessive Aβ production in AD. © 2008.
Keyword β-Secretase
Alzheimer's disease
Oxidative stress
γ-Secretase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 8 August 2008.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Official 2011 Collection
School of Biomedical Sciences Publications
 
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