Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Aging Cell. 2013 Feb;12(1):85-92. doi: 10.1111/acel.12022. Epub 2012 Nov 21.
Increasing evidence demonstrates that amyloid beta (Aβ) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Aβ is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H(2)O(2)-treated PC12 cells. In this study, we reported that HopA might bind to Aβ(1-42) directly and inhibit the Aβ(1-42) aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Aβ(1-42) and Aβ-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.
越来越多的证据表明，β淀粉样蛋白（Aβ）会引起线粒体功能障碍和氧化应激，这有助于阿尔茨海默病（AD）的发病机制。因此，鉴定针对 Aβ 的分子在 AD 的治疗中具有特别重要的意义。从海南龙脑香中获得的具有新型骨架的多酚化合物 hopeahainol A（HopA）在 H 2 O 2 处理的 PC12 细胞中具有潜在的乙酰胆碱酯酶抑制和抗氧化作用。在这项研究中，我们报告说 HopA 可能通过分子动力学模拟、结合测定、透射电子显微镜分析和染色技术直接与 Aβ（1-42）结合并抑制 Aβ（1-42）聚集。我们还表明，HopA 降低了 Aβ（1-42）与 Aβ 结合醇脱氢酶之间的相互作用，这反过来又减少了体内和体外的线粒体功能障碍和氧化应激。此外，HopA 能够通过保护突触功能和减轻 APP/PS1 小鼠的记忆缺陷来挽救长时程增强的诱导。我们的数据表明，HopA 可能是治疗 AD 的一种有前途的药物。
