Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro
Non-steroidal anti-inflammatory drugs have anti-amyloidogenic effects for Alzheimer's β-amyloid fibrils in vitro
复制标题
DOI：
10.1016/j.neuropharm.2005.07.004
复制
发表时间：
2005-12-01
影响因子：
4.7
通讯作者：
Yamada, M
中科院分区：
文献类型：
--
作者：
Hirohata, M;Ono, K;Yamada, M
阿尔茨海默病（AD）的发病机制以淀粉样β肽（AP）和被炎症细胞包围的神经原纤维缠结的脑沉积为特征。长期使用非甾体抗炎药（NSAIDs）可降低。发展为阿尔茨海默病并延缓疾病的发作。在本研究中，我们使用荧光光谱与硫黄酮T和电镜检查非甾体抗炎药如布洛芬、阿司匹林、美氯芬酸钠盐、双氯芬酸钠盐、酮洛芬、氟比洛芬、萘普生、硫磺胺酸和吲哚美辛对β -淀粉样蛋白原纤维（fA β）形成、延伸和不稳定的影响，pH为7.5，体外37℃。所有研究均显示，非甾体抗炎药剂量依赖性地抑制新鲜A β(1-40)和A β(1-42)形成fA β，以及它们的延伸。此外，这些非甾体抗炎药剂量依赖性地破坏了预形成的fA β s的稳定性。所检测的分子的总体活性按以下顺序排列：布洛芬近似于sulindac sulfide >=甲氯芬酸钠盐>阿司匹林近似于酮洛芬>=氟比洛芬近似于双氯芬酸钠盐>萘普生近似于吲哚美辛。尽管这些非甾体抗炎药在体外抑制A β生成fA β和破坏预形成fA β的机制尚不清楚，但非甾体抗炎药可能有望预防和治疗AD。(c) 2005 Elsevier Ltd版权所有。
The pathogenesis of Alzheimer's disease (AD) is characterized by cerebral deposits of amyloid beta-peptides (AP) and neurofibrillary tangles which are surrounded by inflammatory cells. Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of. developing AD and delays the onset of the disease. In the present study, we used fluorescence spectroscopy with thioflavin T and electron microscopy to examine the effects of NSAIDs such as ibuprofen, aspirin, meclofenamic acid sodium salt, diclofenac sodium salt, ketoprofen, flurbiprofen, naproxen, sulindac sulfide and indomethacin on the formation, extension, and destabilization of beta-amyloid fibrils (fA beta) at pH 7.5 at 37 degrees C in vitro. All examined NSAIDs dose-dependently inhibited formation of fA beta from fresh A beta(1-40) and A beta(1-42), as well as their extension. Moreover, these NSAIDs dose-dependently destabilized preformed fA beta s. The overall activity of the molecules examined was in the following order: ibuprofen approximate to sulindac sulfide >= meclofenamic acid sodium salt > aspirin approximate to ketoprofen >= flurbiprofen approximate to diclofenac sodium salt > naproxen approximate to indomethacin. Although the mechanisms by which these NSAIDs inhibit fA beta formation from A beta, and destabilize preformed fA beta in vitro are still unclear, NSAIDs may be promising for the prevention and treatment of AD. (c) 2005 Elsevier Ltd. All rights reserved.