Polyphenols as Potential Metal Chelation Compounds Against Alzheimer's Disease

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-beta (A beta) 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-beta protein precursor (A beta PP) and A beta(42) peptide, affecting A beta 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.

Automated summary

Alzheimer's disease is a common neurodegenerative disease characterized by the aggregation of amyloid-beta, with metal dyshomeostasis playing a critical role in disease progression. Polyphenols, as natural chelators, have therapeutic effects such as antioxidant activity, metal chelation, improvement of mitochondrial function, and inhibition of amyloidogenesis, making them potential candidates for chelation-based therapy for AD.