NOX Activity Is Increased in Mild Cognitive Impairment
NOX Activity Is Increased in Mild Cognitive Impairment
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DOI：
10.1089/ars.2009.2823
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发表时间：
2010-06-01
影响因子：
6.6
通讯作者：
Markesbery, William R.
中科院分区：
文献类型：
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作者：
Bruce-Keller, Annadora J.;Gupta, Sunita;Markesbery, William R.
本研究旨在探讨NADPH氧化酶（NOX）在阿尔茨海默病（AD）临床进展中的作用。具体而言，NOX活性和表达的调节亚基p47（phox）和催化亚基gp 91（phox）进行了评估，在受影响的（上级和颞中回）和未受影响的（小脑）脑区从一个纵向跟踪组的患者。该组包括对照和晚期AD受试者，以及临床前AD和遗忘型轻度认知障碍（MCI）受试者，以评估痴呆早期阶段的NOX谱。数据显示，与对照组相比，MCI患者的颞回中NOX活性和表达显著升高，但在临床前或晚期AD样品中没有，并且在小脑中没有。NOX表达的免疫组织化学评价表明，而小胶质细胞表达高水平的gp 91（phox），中等水平的gp 91（phox）也在神经元中表达。最后，体外实验表明，NOX抑制减弱了寡聚淀粉样β肽损伤培养神经元的能力。总的来说，这些数据表明，NOX的表达和活性上调，特别是在一个脆弱的大脑区域的MCI患者，并建议增加NOX相关的氧化还原途径的神经元可能参与AD的早期发病机制。抗氧化剂。氧化还原信号。12，1371-1382.
This study was undertaken to investigate the profile of NADPH oxidase (NOX) in the clinical progression of Alzheimer's disease (AD). Specifically, NOX activity and expression of the regulatory subunit p47(phox) and the catalytic subunit gp91(phox) was evaluated in affected (superior and middle temporal gyri) and unaffected (cerebellum) brain regions from a longitudinally followed group of patients. This group included both control and late-stage AD subjects, and also subjects with preclinical AD and with amnestic mild cognitive impairment (MCI) to evaluate the profile of NOX in the earliest stages of dementia. Data show significant elevations in NOX activity and expression in the temporal gyri of MCI patients as compared with controls, but not in preclinical or late-stage AD samples, and not in the cerebellum. Immunohistochemical evaluations of NOX expression indicate that whereas microglia express high levels of gp91(phox), moderate levels of gp91(phox) also are expressed in neurons. Finally, in vitro experiments showed that NOX inhibition blunted the ability of oligomeric amyloid beta peptides to injure cultured neurons. Collectively, these data show that NOX expression and activity are upregulated specifically in a vulnerable brain region of MCI patients, and suggest that increases in NOX-associated redox pathways in neurons might participate in the early pathogenesis of AD. Antioxid. Redox Signal. 12, 1371-1382.