Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Curr Opin Chem Biol. 2012 Apr;16(1-2):67-73. doi: 10.1016/j.cbpa.2012.01.016. Epub 2012 Feb 25.
Highly concentrated metals such as Cu, Zn, and Fe are found in amyloid-β (Aβ) plaques within the brain of Alzheimer's disease (AD). In vitro and in vivo studies have suggested that metal binding to Aβ could facilitate Aβ aggregation and generate reactive oxygen species (ROS), which could contribute to the neuropathogenesis of AD. The connection between metal-Aβ interaction/reactivity and AD development, however, has not been clearly revealed owing to the complexity of the disease. In this review, metal-Aβ interaction/reactivity and its relation to neurotoxicity are briefly discussed. Additionally, our review illustrates the recent progress of small molecules, capable of targeting metal-Aβ species and modulating their interaction/reactivity, which could offer a promising approach to interrogate their role in AD.
在阿尔茨海默病(AD)患者大脑的淀粉样蛋白-β(Aβ)斑块中发现了高浓度的金属,如 Cu、Zn 和 Fe。体外和体内研究表明,金属与 Aβ 的结合可以促进 Aβ 聚集并产生活性氧(ROS),这可能有助于 AD 的神经发病机制。然而,由于疾病的复杂性,金属-Aβ 相互作用/反应性与 AD 发展之间的联系尚未被清楚揭示。在这篇综述中,简要讨论了金属-Aβ 相互作用/反应性及其与神经毒性的关系。此外,我们的综述还说明了能够针对金属-Aβ 物种并调节其相互作用/反应性的小分子的最新进展,这为研究它们在 AD 中的作用提供了一种有前途的方法。