Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease

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; Mark P. Mattson

doi:10.1016/j.neurobiolaging.2008.07.003

Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease

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, Mark P. Mattson

Research output: Contribution to journal › Article › peer-review

56 Scopus citations

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.

Original language	English (US)
Pages (from-to)	917-925
Number of pages	9
Journal	Neurobiology of aging
Volume	31
Issue number	6
DOIs	https://doi.org/10.1016/j.neurobiolaging.2008.07.003
State	Published - Jun 2010
Externally published	Yes

Keywords

Alzheimer's disease
Oxidative stress
β-Secretase
γ-Secretase

ASJC Scopus subject areas

Neuroscience(all)
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

Access to Document

10.1016/j.neurobiolaging.2008.07.003

Cite this

Jo, D. G., Arumugam, T. V., Woo, H. N., Park, J. S., Tang, S. C., Mughal, M., Hyun, D. H., Park, J. H., Choi, Y. H., Gwon, A. R., Camandola, S., Cheng, A., Cai, H., Song, W., Markesbery, W. R., & Mattson, M. P. (2010). Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease. Neurobiology of aging, 31(6), 917-925. https://doi.org/10.1016/j.neurobiolaging.2008.07.003

Jo, DG, Arumugam, TV, Woo, HN, Park, JS, Tang, SC, Mughal, M, Hyun, DH, Park, JH, Choi, YH, Gwon, AR, Camandola, S, Cheng, A, Cai, H, Song, W, Markesbery, WR & Mattson, MP 2010, 'Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease', Neurobiology of aging, vol. 31, no. 6, pp. 917-925. https://doi.org/10.1016/j.neurobiolaging.2008.07.003

@article{442b60b10e2440a19d60c17fe1ecd34e,

title = "Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease",

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.",

keywords = "Alzheimer's disease, Oxidative stress, β-Secretase, γ-Secretase",

author = "Jo, {Dong Gyu} and Arumugam, {Thiruma V.} and Woo, {Ha Na} and Park, {Jong Sung} and Tang, {Sung Chun} and Mohamed Mughal and Hyun, {Dong Hoon} and Park, {Jun Hyung} and Choi, {Yun Hyung} and Gwon, {A. Ryeong} and Simonetta Camandola and Aiwu Cheng and Huaibin Cai and Weihong Song and Markesbery, {William R.} and Mattson, {Mark P.}",

note = "Funding Information: This research was supported by the Intramural Research Program of the National Institute on Aging, NIH, and by a Korea Research Foundation Grant to D.-G.J. (MOEHRD, Basic Research Promotion Fund) (KRF-2007-313-C00526).",

year = "2010",

month = jun,

doi = "10.1016/j.neurobiolaging.2008.07.003",

language = "English (US)",

volume = "31",

pages = "917--925",

journal = "Neurobiology of aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

number = "6",

}

TY - JOUR

T1 - Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease

AU - Jo, Dong Gyu

AU - Arumugam, Thiruma V.

AU - Woo, Ha Na

AU - Park, Jong Sung

AU - Tang, Sung Chun

AU - Mughal, Mohamed

AU - Hyun, Dong Hoon

AU - Park, Jun Hyung

AU - Choi, Yun Hyung

AU - Gwon, A. Ryeong

AU - Camandola, Simonetta

AU - Cheng, Aiwu

AU - Cai, Huaibin

AU - Song, Weihong

AU - Markesbery, William R.

AU - Mattson, Mark P.

N1 - Funding Information: This research was supported by the Intramural Research Program of the National Institute on Aging, NIH, and by a Korea Research Foundation Grant to D.-G.J. (MOEHRD, Basic Research Promotion Fund) (KRF-2007-313-C00526).

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Oxidative stress

KW - β-Secretase

KW - γ-Secretase

UR - http://www.scopus.com/inward/record.url?scp=77951975308&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951975308&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2008.07.003

DO - 10.1016/j.neurobiolaging.2008.07.003

M3 - Article

C2 - 18687504

AN - SCOPUS:77951975308

SN - 0197-4580

VL - 31

SP - 917

EP - 925

JO - Neurobiology of aging

JF - Neurobiology of aging

IS - 6

ER -

Evidence that γ-secretase mediates oxidative stress-induced β-secretase expression in Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this