药学学报, 2013, 48(12): 1743-1754
沈娇宁, 徐刘昕, 王蕊. 环氧合酶、脂氧酶及其靶向药物与阿尔茨海默病的防治[J]. 药学学报, 2013, 48(12): 1743-1754.
SHEN Jiao-ning, XU Liu-xin, WANG Rui. Cyclooxygenases, lipoxygenases, their targeted drugs and the prevention of Alzheimer’s disease[J]. Acta Pharmaceutica Sinica, 2013, 48(12): 1743-1754.

沈娇宁, 徐刘昕, 王蕊
华东理工大学药学院, 上海市新药设计重点实验室, 上海 200237
许多研究显示,炎症与阿尔茨海默病(Alzheimer’s disease,AD)的发生发展关系密切。有证据表明长期服用非甾体抗炎药(non-steroidal anti-inflammatory drugs,NSAIDs)能够减轻AD病人或老年人认知能力的 下降。花生四烯酸(arachidonic acid,AA)代谢网络所产生的炎症介质,与很多炎症相关的疾病有关。脂氧酶(lipoxygenase,LOX)和环氧合酶(cyclooxygenase,COX)是AA网络中的两个关键酶,它们催化产生的类花生酸类物质(eicosanoids)有重要的促炎功能和许多生物活性,对AD的进程产生重要影响。虽然尚有不同的观点及互相矛盾的证据,但COX与LOX仍是当前研究AD发病机制和治疗药物的热点领域。本文主要对近年COX和LOX研究进展,尤其是与中枢神经系统功能及与AD发病的关系,以及LOX和COX作为药物干预靶点用于防治AD的可能性进行综述。
关键词:    脂氧酶      环氧合酶      花生四烯酸      阿尔茨海默病      β-淀粉样蛋白     
Cyclooxygenases, lipoxygenases, their targeted drugs and the prevention of Alzheimer’s disease
SHEN Jiao-ning, XU Liu-xin, WANG Rui
School of Pharmacy, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China
Many studies have shown that chronic inflammation occurs in the brain of patients with Alzheimer's disease (AD). It is well known that long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive decline of AD patient and elderly. Several inflammatory cytokines produced in the metabolism of arachidonic acid (AA) are closely related to inflammatory diseases. Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA network, the products eicosanoids have an important impact on the progression of AD. Although there are many arguments and conflicting evidence, currently LOXs and COXs are still the hot topics in the research on AD pathogenesis and drug development. Here, we review the progress in research on COXs and LOXs, including their actions on CNS and their association with AD, and explore the feasibility of LOXs and COXs as targets for the drugs to prevent and/or treat AD.
Key words:    lipoxygenase    cyclooxygenase    arachidonic acid    Alzheimer’s disease    Aβ   
收稿日期: 2013-07-12
基金项目: 国家自然科学基金资助项目(81072627);教育部111项目(B07023);浦江人才计划(11PJ1402300);上海市科学技术委员会上海市新药设计重点实验室资助项目(11DZ2260600);上海市科学技术委员会重点项目(12431900901).
通讯作者: 王蕊
Email: ruiwang@ecust.edu.cn
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