Feng Jiahao, She Yifei, Li Chongjia, Shen Lei
Key Laboratory for Neurodegenerative Diseases Nanomedicine of Hubei Province, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China.
Key Laboratory for Neurodegenerative Diseases Nanomedicine of Hubei Province, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China.
Adv Colloid Interface Sci. 2023 Oct;320:103009. doi: 10.1016/j.cis.2023.103009. Epub 2023 Sep 25.
Although the pathogenesis of Alzheimer's disease (AD) is still unclear, abnormally high concentrations of metal ions, like copper, iron and zinc, were found in senile plaques of AD brain, which inspires extensive studies on the fundamental molecular interactions of metal ions with the pathogenic hallmarks, amyloid-β (Aβ) peptides and tau proteins, respectively forming senile plaques and neurofibrillary tangles (NFTs) in AD brains. Early works concern the concentration effect of the metal ions on Aβ and tau aggregation. Yet, it is obvious that the surrounding environment of the metal ions must also be considered, not just the metal ions as free accessible forms in the solution phase. The most important surrounding environment in vivo is a very large surface area from cell membranes and other macromolecular surfaces. These bio-interfaces make the kinetic pathways of metal ion mediated Aβ and tau aggregation radically different from those in the solution phase. To better understand the role of metal ions in AD peptide and protein aggregation, we summarize and discuss the recent achievements in the research of metal ion mediated Aβ and tau aggregation, particularly the corresponding mechanism differences between the solution phase and the surface environment. The metal ion chelation therapy for AD is also discussed from the point of the surface pool of metal ions.
尽管阿尔茨海默病（AD）的发病机制仍不明确，但在AD大脑的老年斑中发现了异常高浓度的金属离子，如铜、铁和锌，这激发了人们对金属离子与致病标志物淀粉样β（Aβ）肽和tau蛋白之间基本分子相互作用的广泛研究，它们分别在AD大脑中形成老年斑和神经原纤维缠结（NFTs）。早期研究关注金属离子对Aβ和tau聚集的浓度效应。然而，显然金属离子的周围环境也必须考虑，而不仅仅是溶液相中可自由获取的金属离子形式。体内最重要的周围环境是来自细胞膜和其他大分子表面的非常大的表面积。这些生物界面使金属离子介导的Aβ和tau聚集的动力学途径与溶液相中的截然不同。为了更好地理解金属离子在AD肽和蛋白质聚集中的作用，我们总结并讨论了金属离子介导的Aβ和tau聚集研究的最新成果，特别是溶液相和表面环境之间相应的机制差异。还从金属离子表面池的角度讨论了AD的金属离子螯合疗法。
