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

被引：81

作者：

Jo, Dong-Gyu ^{[1
,2
]}

Arumugam, Thiruma V. ^{[1
]}

Woo, Ha-Na ^{[2
]}

Park, Jong-Sung ^{[2
]}

Tang, Sung-Chun ^{[1
,3
]}

Mughal, Mohamed ^{[1
]}

Hyun, Dong-Hoon ^{[1
,4
]}

Park, Jun-Hyung ^{[2
]}

Choi, Yun-Hyung ^{[2
]}

Gwon, A-Ryeong ^{[2
]}

Camandola, Simonetta ^{[1
]}

Cheng, Aiwu ^{[1
]}

Cai, Huaibin ^{[5
,6
]}

Song, Weihong ^{[7
]}

Markesbery, William R. ^{[8
]}

Mattson, Mark P. ^{[1
,9
]}

机构：

[1] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA

[2] Sungkyunkwan Univ, Coll Pharm, Suwon, South Korea

[3] Natl Taiwan Univ Hosp, Stroke Ctr, Dept Neurol, Taipei, Taiwan

[4] Ewha Womans Univ, Div Mol Life Sci, Seoul, South Korea

[5] Univ British Columbia, Dept Psychiat, Brain Res Ctr, Vancouver, BC V5Z 1M9, Canada

[6] Univ British Columbia, Grad Program Neurosci, Vancouver, BC V5Z 1M9, Canada

[7] NIA, Neurogenet Lab, Bethesda, MD 20892 USA

[8] Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY USA

[9] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

来源：

NEUROBIOLOGY OF AGING | 2010年 / 31卷 / 06期

关键词：

beta-Secretase; Alzheimer's disease; Oxidative stress; gamma-Secretase; AMYLOID PRECURSOR PROTEIN; DEPENDENT TRANSCRIPTIONAL CONTROL; DEGRADING ENZYME NEPRILYSIN; LIPID-PEROXIDATION; A-BETA; INTRACELLULAR DOMAINS; FREE-RADICALS; BACE1; COMPLEXES; TRANSPORT;

D O I：

10.1016/j.neurobiolaging.2008.07.003

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

B-Secretase (BACE I), an enzyme responsible for the production of amyloid p-peptide (AB), 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 BACE I expression in presenilin-I (gamma-secretase)-deficient cells and in normal cells treated with gamma-secretase inhibitors. Oxidative stress-induced B-secretase activity and sAPPB levels were suppressed by gamma-secretase inhibitors. Levels of and beta-secretase activities were greater in brain tissue samples from AD patients compared to non-demented control subjects, and the elevated BACE I level in the brains of 3xTgAD mice was reduced by treatment with a gamma-secretase inhilitor. Our findings suggest that gamma-secretase mediates oxidative stress-induced expression of BACE I resulting in excessive AB production in AD. Published by Elsevier Inc.

引用

页码：917 / 925

页数：9

共 31 条

[21] Triple-transgenic model of Alzheimer's disease with plaques and tangles:: Intracellular Aβ and synaptic dysfunction [J].

Oddo, S ;

Caccamo, A ;

Shepherd, JD ;

Murphy, MP ;

Golde, TE ;

Kayed, R ;

Metherate, R ;

Mattson, MP ;

Akbari, Y ;

LaFerla, FM .

NEURON, 2003, 39 (03) :409-421

[22] Presenilin-dependent transcriptional control of the Aβ-degrading enzyme neprilysin by intracellular domains of βAPP and APLP [J].

Pardossi-Piquard, R ;

Petit, A ;

Kawarai, T ;

Sunyach, C ;

da Costa, CA ;

Vincent, B ;

Ring, S ;

D'Adamio, L ;

Shen, J ;

Müller, U ;

Hyslop, PS ;

Checler, F .

NEURON, 2005, 46 (04) :541-554

[23] Presenilin diversifies its portfolio [J].

Parks, Annette L. ;

Curtis, Daniel .

TRENDS IN GENETICS, 2007, 23 (03) :140-150

[24] Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis [J].

Praticò, D ;

Uryu, K ;

Leight, S ;

Trojanowswki, JQ ;

Lee, VMY .

JOURNAL OF NEUROSCIENCE, 2001, 21 (12) :4183-4187

[25]

Praticò D, 2000, ANN NEUROL, V48, P809, DOI 10.1002/1531-8249(200011)48:5<809::AID-ANA19>3.3.CO

[26]

2-0

[27] Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression [J].

Sun, Xiulian ;

He, Guiqiong ;

Qing, Hong ;

Zhou, Weihui ;

Dobie, Frederick ;

Cai, Fang ;

Staufenbiel, Matthias ;

Huang, L. Eric ;

Song, Weihong .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (49) :18727-18732

[28] Oxidative stress increases expression and activity of BACE in NT2 neurons [J].

Tamagno, E ;

Bardini, P ;

Obbili, A ;

Vitali, A ;

Borghi, R ;

Zaccheo, D ;

Pronzato, MA ;

Danni, O ;

Smith, MA ;

Perry, G ;

Tabaton, M .

NEUROBIOLOGY OF DISEASE, 2002, 10 (03) :279-288

[29] Oxidative stress activates a positive feedback between the γ- and β-secretase cleavages of the β-amyloid precursor protein [J].

Tamagno, Elena ;

Guglielmotto, Michela ;

Aragno, Manuela ;

Borghi, Roberta ;

Autelli, Riccardo ;

Giliberto, Luca ;

Muraca, Giuseppe ;

Danni, Oliviero ;

Zhu, Xiongwei ;

Smith, Mark A. ;

Perry, George ;

Jo, Dong-Gyu ;

Mattson, Mark P. ;

Tabaton, Massimo .

JOURNAL OF NEUROCHEMISTRY, 2008, 104 (03) :683-695

[30] The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor [J].

von Rotz, RC ;

Kohli, BM ;

Bosset, J ;

Meier, M ;

Suzuki, T ;

Nitsch, RM ;

Konietzko, U .

JOURNAL OF CELL SCIENCE, 2004, 117 (19) :4435-4448

← 1 2 3 4 →