Department of Neurology and Neurobiology and Aging, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
J Biol Chem. 2012 Apr 27;287(18):14631-43. doi: 10.1074/jbc.M111.325456. Epub 2012 Mar 5.
Cerebral deposition of amyloid β protein (Aβ) is an invariant feature of Alzheimer disease (AD), and epidemiological evidence suggests that moderate consumption of foods enriched with phenolic compounds reduce the incidence of AD. We reported previously that the phenolic compounds myricetin (Myr) and rosmarinic acid (RA) inhibited Aβ aggregation in vitro and in vivo. To elucidate a mechanistic basis for these results, we analyzed the effects of five phenolic compounds in the Aβ aggregation process and in oligomer-induced synaptic toxicities. We now report that the phenolic compounds blocked Aβ oligomerization, and Myr promoted significant NMR chemical shift changes of monomeric Aβ. Both Myr and RA reduced cellular toxicity and synaptic dysfunction of the Aβ oligomers. These results suggest that Myr and RA may play key roles in blocking the toxicity and early assembly processes associated with Aβ through different binding.
淀粉样蛋白β 蛋白（Aβ）在大脑中的沉积是阿尔茨海默病（AD）的一个不变特征，流行病学证据表明，适量食用富含酚类化合物的食物可降低 AD 的发病率。我们之前曾报道过，酚类化合物杨梅素（Myr）和迷迭香酸（RA）可抑制 Aβ 的体外和体内聚集。为了阐明这些结果的机制基础，我们分析了五种酚类化合物在 Aβ 聚集过程中和寡聚体诱导的突触毒性中的作用。我们现在报告说，这些酚类化合物阻止了 Aβ 的寡聚化，并且 Myr 促进了单体 Aβ 的显著 NMR 化学位移变化。Myr 和 RA 均降低了 Aβ 寡聚物的细胞毒性和突触功能障碍。这些结果表明，Myr 和 RA 可能通过不同的结合方式在阻止与 Aβ 相关的毒性和早期组装过程中发挥关键作用。
