Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex
Cyclin D1 and cyclin E are co-localized with cyclo-oxygenase 2 (COX-2) in pyramidal neurons in Alzheimer disease temporal cortex
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DOI：
10.1093/jnen/61.8.678
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发表时间：
2002-08-01
影响因子：
3.2
通讯作者：
Arendt, T
中科院分区：
文献类型：
--
作者：
Hoozemans, JJM;Brückner, MK;Arendt, T
定期使用非类固醇抗炎药(NSAIDs)似乎可以减缓几种疾病的进展，包括结肠癌、肺癌、乳腺癌和阿尔茨海默病(AD)。一些研究表明，非甾体抗炎药可以调节细胞周期进程，特别是在G0/G1期。大多数非甾体抗炎药的主要靶点是环氧合酶(COX)，它以COX-1和COX-2两种亚型存在。在AD和非痴呆对照脑组织中，COX-2在神经细胞中表达。本研究在免疫组织化学水平上研究了环氧合酶-2、细胞周期蛋白D1和细胞周期蛋白E在AD和非痴呆对照组颞叶皮质中的表达。环氧合酶-2、细胞周期蛋白D1和细胞周期蛋白E在AD患者和正常对照组锥体神经元中均有表达。环氧合酶-2免疫阳性神经元的数目与细胞周期蛋白E和细胞周期蛋白D1阳性神经元的数目呈正相关。连续组织切片免疫组织化学染色和免疫荧光双标记法显示，COX-2和细胞周期蛋白D_1、E在神经细胞中共表达。此外，环氧合酶-2和细胞周期蛋白E的神经元表达与淀粉样蛋白P沉积的Braak评分呈负相关。我们的发现提示COX-2的神经元表达与细胞周期标记物之间的关系，这可能参与AD的早期病理。
Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) seems to reduce the progression of several diseases, including colon cancer, lung cancer, breast cancer and Alzheimer disease (AD). Several studies have shown that NSAIDs can modulate cell cycle progression, especially in the G0/G1 phase. The main target of most NSAIDs is the enzyme cyclooxygenase (COX), which occurs in 2 isoforms, COX-1 and COX-2. In AD and non-demented control brain, COX-2 is expressed in neuronal cells. In this study the expression of COX-2, cyclin D1, and cyclin E was investigated at the immunohistochemical level in AD and non-demented control temporal cortex. COX-2, cyclin D1, and cyclin E expression was detected in pyramidal neurons in both AD and control patients. The number of COX-2-immumoreactive neurons positively correlated with the number of cyclin E- and cyclin D1-immunoreactive neurons. Moreover, immunostaining of sequential tissue sections and double immunofluorescence labeling revealed co-expression of COX-2 and cyclin D1 and E in neuronal cells. In addition, an inverse correlation was observed between the neuronal expression of COX-2 and cyclin E and the Braak score for amyloid P deposits. Our findings suggest a relationship between the neuronal expression of COX-2 and cell cycle markers, which may be involved early in AD pathology.