Alzheimer's disease (AD) is the most common neurodegenerative disease affecting more than 50 million people worldwide. The pathology of this multifactorial disease is primarily characterized by the formation of amyloid-β (Aβ) aggregates; however, other etiological factors including metal dyshomeostasis, specifically copper (Cu), zinc (Zn), and iron (Fe), play critical role in disease progression. Because these transition metal ions are important for cellular function, their imbalance can cause oxidative stress that leads to cellular death and eventual cognitive decay. Importantly, these transition metal ions can interact with the amyloid-β protein precursor (AβPP) and Aβ42 peptide, affecting Aβ aggregation and increasing its neurotoxicity. Considering how metal dyshomeostasis may substantially contribute to AD, this review discusses polyphenols and the underlying chemical principles that may enable them to act as natural chelators. Furthermore, polyphenols have various therapeutic effects, including antioxidant activity, metal chelation, mitochondrial function, and anti-amyloidogenic activity. These combined therapeutic effects of polyphenols make them strong candidates for a moderate chelation-based therapy for AD.

中文翻译：

---

多酚作为潜在的金属螯合化合物对抗阿尔茨海默病。

阿尔茨海默病 (AD) 是最常见的神经退行性疾病，影响全球超过 5000 万人。这种多因素疾病的病理学主要特征是淀粉样蛋白-β (Aβ) 聚集体的形成；然而，其他病因，包括金属体内平衡失调，特别是铜 (Cu)、锌 (Zn) 和铁 (Fe)，在疾病进展中发挥着关键作用。由于这些过渡金属离子对细胞功能很重要，因此它们的不平衡会引起氧化应激，从而导致细胞死亡并最终导致认知衰退。重要的是，这些过渡金属离子可以与淀粉样β蛋白前体（AβPP）和Aβ42肽相互作用，影响Aβ聚集并增加其神经毒性。考虑到金属动态平衡失调可能对 AD 产生重大影响，这篇综述讨论了多酚以及可能使它们充当天然螯合剂的基本化学原理。此外，多酚具有多种治疗作用，包括抗氧化活性、金属螯合、线粒体功能和抗淀粉样蛋白生成活性。多酚的这些综合治疗作用使它们成为 AD 中度螯合疗法的有力候选者。