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 peopleworldwide. The pathology of this multi factorial disease is primarily characterized by the formation of amyloid-NL (ANL)aggregates; however, other etiological factors including metal dyshomeostasis, specifically copper (Cu), zinc (Zn), andiron (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, thesetransition metal ions can interact with the amyloid-NLprotein precursor (ANLPP) and ANL 42 peptide, affecting ANL aggregationand increasing its neurotoxicity. Considering how metal dyshomeostasis may substantially contribute to AD, this reviewdiscusses 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, andanti-amyloidogenic activity. These combined therapeutic effects of polyphenols make them strong candidates for a moderatechelation-based therapy for AD.