School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
Neurochem Int. 2012 Dec;61(7):1192-201. doi: 10.1016/j.neuint.2012.08.012. Epub 2012 Sep 7.
As currently understood, Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is driven by the aggregation of amyloid beta (Aβ) protein. It has been shown that resveratrol (RES) may attenuate amyloid β peptide-induced toxicity, promote Aβ clearance and reduce senile plaques. However, it remains to be determined whether RES could interact directly with Aβ. The aim of the present study was to examine the direct binding of RES to monomer and fibril Aβ. Using surface plasmon resonance (SPR) and proton nuclear magnetic resonance ((1)H NMR), our results identified the direct binding of RES to Aβ. The ability of RES to bind to both fibril and monomer Aβ(1-40 and 1-42) was further analyzed by SPR. The binding response of RES to fAβ(1-42) was higher than that to monomer Aβ(1-42), whereas the binding response of RES to fAβ(1-40) was lower than that to monomer Aβ(1-40). The K(D) of RES for fibril Aβ(1-40 or 1-42) was higher than that for the corresponding monomer Aβ. Compared to the control compound Congo red (CR), the binding responses of RES to monomer Aβ(1-42) and Aβ(1-40) were stronger, but binding to fibril Aβ(1-42) was weaker, and the K(D)s of RES with both monomer and fibril Aβ(1-40) and Aβ(1-42) were higher than that of CR. When Aβ(1-40 or 1-42) was co-incubated with RES (50μM), the thioflavin T fluorescence of the mixture was weakened, and the number and length of amyloid fibrils were decreased. Furthermore, the results of staining in consecutive brain slices from AD patients showed that RES (10(-4)M) could stain senile plaques. These results indicated that RES could bind directly to Aβ in different states, which may provide new insight into the protective properties of RES against AD.
目前认为，阿尔茨海默病（AD）是一种慢性神经退行性疾病，由淀粉样β（Aβ）蛋白聚集驱动。已经表明白藜芦醇（RES）可以减轻淀粉样β肽诱导的毒性，促进 Aβ 清除并减少老年斑。然而，尚不确定 RES 是否可以与 Aβ 直接相互作用。本研究的目的是研究 RES 与单体和纤维 Aβ 的直接结合。使用表面等离子体共振（SPR）和质子核磁共振（1H NMR），我们的结果确定了 RES 与 Aβ 的直接结合。进一步通过 SPR 分析了 RES 与纤维和单体 Aβ（1-40 和 1-42）的结合能力。RES 与 fAβ（1-42）的结合反应高于与单体 Aβ（1-42）的结合反应，而 RES 与 fAβ（1-40）的结合反应低于与单体 Aβ（1-40）的结合反应。RES 对 fAβ（1-40 或 1-42）的 K(D)高于相应单体 Aβ 的 K(D)。与对照化合物刚果红（CR）相比，RES 对单体 Aβ（1-42）和 Aβ（1-40）的结合反应更强，但对纤维 Aβ（1-42）的结合反应较弱，并且 RES 与单体和纤维 Aβ（1-40）和 Aβ（1-42）的 K(D)均高于 CR。当 Aβ（1-40 或 1-42）与 RES（50μM）共孵育时，混合物的硫黄素 T 荧光减弱，并且纤维数量和长度减少。此外，来自 AD 患者的连续脑切片染色的结果表明 RES（10（-4）M）可以染色老年斑。这些结果表明 RES 可以直接与不同状态的 Aβ 结合，这可能为 RES 对 AD 的保护特性提供新的见解。
