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

Abstract

The link between bio-metals, Alzheimer's disease ( AD ) , and its associated protein, amyloid- β( A β) , 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 β. Dyshomeostasis of metal ions and their interaction with A βhas largely been implicated in AD. Copper plays a crucial role in amyloid- βtoxicity, and AD development potentially occurs through direct interaction with the copper-binding motif of APP and different amino acid residues of A β. Previous reports suggest that high levels of copper accumulation in the AD brain result in modulation of toxic A βpeptide 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 β, which accelerate s the kinetics of fibril formation and promote amyloid- βmediated cell toxicity in Alzheimer's disease and the potential use of various copper chelators in the prevention of copper-mediated A βtoxicity.