Nuclear factor erythroid 2-related factor 2 protects against beta amyloid

被引：227

作者：

Kanninen, Katja ^{[1
,3
]}

Malm, Tarja M. ^{[1
,3
]}

Jyrkkanen, Henna-Kaisa ^{[2
,3
]}

Goldsteins, Gundars ^{[1
,3
]}

Keksa-Goldsteine, Velta ^{[1
,3
]}

Tanila, Heikki ^{[1
,3
]}

Yamamoto, Masayuki ^{[5
,6
,7
]}

Yla-Herttuala, Seppo ^{[2
,3
]}

Levonen, Anna-Liisa ^{[2
,3
]}

Koistinaho, Jari ^{[1
,3
,4
]}

机构：

[1] Univ Kuopio, AI Virtanen Inst Mol Sci, Dept Neurobiol, FIN-70211 Kuopio, Finland

[2] Univ Kuopio, AI Virtanen Inst Mol Sci, Dept Biotechnol & Mol Med, FIN-70211 Kuopio, Finland

[3] Univ Kuopio, Bioctr Kuopio, FIN-70211 Kuopio, Finland

[4] Kuopio Univ Hosp, Dept Oncol, Kuopio 70211, Finland

[5] Univ Tsukuba, Ctr TARA, Tsukuba, Ibaraki 3058577, Japan

[6] Univ Tsukuba, JST ERATO Environm Response Project, Tsukuba, Ibaraki 3058577, Japan

[7] Tohoku Univ, Grad Sch Med, Dept Med Biochem, Aoba Ku, Sendai, Miyagi 9808575, Japan

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2008年 / 39卷 / 03期

关键词：

Gene transfer; Neuroprotection; Oxidative stress; Transgenic; Knock-out;

D O I：

10.1016/j.mcn.2008.07.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Nuclear factor erythroid 2-related factor 2 (Nrf2) coordinates the up-regulation of cytoprotective genes via the antioxidant response element (ARE). In the pathogenesis of Alzheimer's disease (AD) current evidence supports the role of oxidative stress. Considering the protective role of Nrf2 against oxidative injury, we studied Nrf2 and Nrf2-ARE target genes in transgenic AD mice and tested whether Nrf2 could confer neuroprotection against amyloid-beta peptides (A beta). Nrf2-ARE pathway was attenuated in APP/PS1 transgenic mouse brain at the time of A beta deposition. Boosting the activity of the Nrf2-ARE pathway by tert-butylhydroquinone treatment or adenoviral Nrf2 gene transfer protected against A beta toxicity. This neuroprotection was associated with increased expression of Nrf2 target genes and reduced phosphorylation of p66Shc, a marker of increased susceptibility for oxidative stress. The findings suggest that the Nrf2-ARE pathway may be impaired in AD and that induction of the Nrf2-ARE defence mechanism may prevent or delay AD-like pathology. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：302 / 313

页数：12

共 66 条

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