Shimohama S, Tanino H, Kawakami N, Okamura N, Kodama H, Yamaguchi T, Hayakawa T, Nunomura A, Chiba S, Perry G, Smith M A, Fujimoto S
Department of Neurology, Kyoto University, Kyoto, 606-8507, Japan.
Biochem Biophys Res Commun. 2000 Jun 24;273(1):5-9. doi: 10.1006/bbrc.2000.2897.
The present study is the first to show that superoxide (O(-)(2)) forming NADPH oxidase is activated in Alzheimer's disease (AD) brains by demonstrating the marked translocation of the cytosolic factors p47-phox and p67-phox to the membrane. In conjunction with a recent in vitro study showing that amyloid beta activates O(-)(2) forming NADPH oxidase in microglia, where these phox proteins are localized in this study, the present results suggest that, in AD, NADPH oxidase is activated in microglia, resulting in the formation of reactive oxygen species which can be toxic to neighboring neurons in AD.
本研究首次表明，通过证明胞质因子p47-吞噬氧化蛋白和p67-吞噬氧化蛋白向膜的显著易位，在阿尔茨海默病（AD）大脑中形成超氧化物（O(-)(2)）的NADPH氧化酶被激活。结合最近一项体外研究表明，淀粉样β蛋白在小胶质细胞中激活形成O(-)(2)的NADPH氧化酶，而在本研究中这些吞噬氧化蛋白定位于小胶质细胞，目前的结果表明，在AD中，NADPH氧化酶在小胶质细胞中被激活，导致活性氧的形成，而活性氧对AD中的邻近神经元可能有毒性。
