Prostaglandin H2 (PGH2) accelerates formation of amyloid β1-42 oligomers
Prostaglandin H2 (PGH2) accelerates formation of amyloid β1-42 oligomers
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DOI：
10.1046/j.1471-4159.2002.01064.x
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发表时间：
2002-08-01
影响因子：
4.7
通讯作者：
Oates, JA
中科院分区：
文献类型：
--
作者：
Boutaud, O;Ou, JJ;Oates, JA
流行病学证据表明，环氧合酶活性与阿尔茨海默病的发病机制有关，在阿尔茨海默病中，已发现淀粉样蛋白斑块含有增加水平的淀粉样蛋白β肽的二聚体和更高水平的多聚体。花生四烯酸被环加氧酶氧化的产物前列腺素H-2（PGH（2）），非酶促重排为几种甘草定，包括高活性的γ-酮醛，左旋甘草定E-2和D-2。我们证明PGH（2）显著加速淀粉样β（1-42）二聚体和高级寡聚体的形成。这与肽的左旋兰素加合物的形成有关。这些发现为环加氧酶活性与β淀粉样蛋白低聚物形成相关的假说提供了分子基础。
Epidemiologic evidence implicates cyclooxygenase activity in the pathogenesis of Alzheimer's disease, in which amyloid plaques have been found to contain increased levels of dimers and higher multimers of the amyloid beta peptide. The product of the oxygenation of arachidonic acid by the cyclooxygenases, prostaglandin H-2 (PGH(2) ), rearranges non-enzymatically to several prostaglandins, including the highly reactive gamma-keto aldehydes, levuglandins E-2 and D-2 . We demonstrate that PGH(2) markedly accelerates the formation of dimers and higher oligomers of amyloid beta(1-42) . This is associated with the formation of levuglandin adducts of the peptide. These findings provide the molecular basis for a hypothesis linking cyclooxygenase activity to the formation of oligomers of amyloid beta.