• Dong-Gyu Jo, Thiruma V Arumugam, Ha-Na Woo, Jong-Sung Park, Sung-Chun Tang, Mohamed Mughal, Dong-Hoon Hyun, Jun-Hyung Park, Yun-Hyung Choi, A-Ryeong Gwon, Simonetta Camandola, Aiwu Cheng, Huaibin Cai, Weihong Song, William R Markesbery, and Mark P Mattson.
• Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, Baltimore, MD 21224, USA.
• Neurobiol. Aging. 2010 Jun 1; 31 (6): 917-25.

AbstractBeta-secretase (BACE1), an enzyme responsible for the production of amyloid beta-peptide (Abeta), 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 (gamma-secretase)-deficient cells and in normal cells treated with gamma-secretase inhibitors. Oxidative stress-induced beta-secretase activity and sAPPbeta levels were suppressed by gamma-secretase inhibitors. Levels of gamma- and beta-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 gamma-secretase inhibitor. Our findings suggest that gamma-secretase mediates oxidative stress-induced expression of BACE1 resulting in excessive Abeta production in AD.Published by Elsevier Inc.

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