Copper-mediated β-amyloid toxicity and its chelation therapy in Alzheimer's disease

The link between bio-metals, Alzheimer's disease (AD), and its associated protein, amyloid-beta (A beta), is very complex and one of the most studied aspects currently. Alzheimer's disease, a progressive neurodegenerative disease, is proposed to occurs due to the misfolding and aggregation of A beta. Dyshomeostasis of metal ions and their interaction with A beta has largely been implicated in AD. Copper plays a crucial role in amyloid-beta toxicity, and AD development potentially occurs through direct interaction with the copper-binding motif of APP and different amino acid residues of A beta. Previous reports suggest that high levels of copper accumulation in the AD brain result in modulation of toxic A beta peptide levels, implicating the role of copper in the pathophysiology of AD. In this review, we explore the possible mode of copper ion interaction with A beta, which accelerates the kinetics of fibril formation and promote amyloid-beta mediated cell toxicity in Alzheimer's disease and the potential use of various copper chelators in the prevention of copper-mediated A beta toxicity.

Automated summary

The link between bio-metals, Alzheimer's disease, and A beta protein is very complex, and copper plays a crucial role in amyloid-beta toxicity and AD development. High levels of copper accumulation in the AD brain result in modulation of toxic A beta peptide levels, and the interaction between copper and A beta contributes to the pathophysiology of AD.