Cognitive impairment in humanized APP×PS1 mice is linked to Aβ(1-42) and NOX activation.
Cognitive impairment in humanized APP×PS1 mice is linked to Aβ(1-42) and NOX activation.
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DOI：
10.1016/j.nbd.2011.07.012
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发表时间：
2011-12
影响因子：
6.1
通讯作者：
Keller, Jeffrey N.
中科院分区：
文献类型：
--
作者：
Bruce-Keller, Annadora J.;Gupta, Sunita;Knight, Alecia G.;Beckett, Tina L.;McMullen, Jessica M.;Davis, Paulina R.;Murphy, M. Paul;Van Eldik, Linda J.;St Clair, Daret;Keller, Jeffrey N.
阿尔茨海默病（AD）的认知功能障碍与淀粉样β肽的广泛沉积和氧化应激密切相关，但这些指标在痴呆发展中的确切作用尚不清楚。本研究旨在确定年龄增长的人源化APP × PS1基因敲入小鼠中认知障碍、自由基产生酶NADPH氧化酶（NOX）活化与Aβ沉积和溶解度进行性变化之间的关系。数据显示，在老化的APP × PS1小鼠中，认知性能和关键突触蛋白的表达逐渐降低。APP × PS1小鼠的NOX活性和NOX亚基NOX 4的表达也随着年龄的增长而显著增加，NOX活性与认知功能障碍呈显著的线性关系。数据进一步表明，在APP × PS1基因敲入小鼠中，Aβ1-42的年龄依赖性增加与NOX活性和认知能力均具有显著的线性关系。总的来说，这些数据表明，在Aβ发病机制的人源化模型中，NOX表达和活性随着年龄的增长而显著上调，并表明NOX相关的氧化还原途径与认知功能丧失和Aβ1-42沉积密切相关。
Cognitive impairment in Alzheimer’s disease (AD) is strongly associated with both extensive deposition of amyloid β peptides and oxidative stress, but the exact role of these indices in the development of dementia is not clear. This study was designed to determine the relationship between cognitive impairment, activation of the free radical producing enzyme NADPH oxidase (NOX), and progressive changes in Aβ deposition and solubility in humanized APP × PS1 knock-in mice of increasing age. Data show that cognitive performance and expression of key synaptic proteins was progressively decreased in aging APP × PS1 mice. Likewise, NOX activity and expression of the specific NOX subunit NOX4 was significantly increased in APP × PS1 mice in an age-dependent manner, and NOX activity and cognitive impairment shared a significant linear relationship. Data further show that age-dependent increases in Aβ1-42 had a significant linear relationship with both NOX activity and cognitive performance in APP × PS1 knock-in mice. Collectively, these data show that NOX expression and activity are significantly upregulated with age in this humanized model of Aβ pathogenesis, and suggest that NOX-associated redox pathways are intimately linked to both the loss of cognitive function and the deposition of Aβ1-42.
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影响因子：
2.4
作者：
Block, Michelle L.
通讯作者：
Block, Michelle L.
影响因子：
6.6
作者：
Bruce-Keller, Annadora J.;Gupta, Sunita;Markesbery, William R.
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作者：
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Markesbery, WR
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作者：
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Butterfield, D. Allan
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作者：
Hu, DY;Serrano, F;Klann, E
通讯作者：
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