CuII Binding Properties of N-Truncated Aβ Peptides: In Search of Biological Function

As life expectancy increases, the number of people affected by progressive and irreversible dementia, Alzheimers Disease (AD), is predicted to grow. No drug designs seem to be working in humans, apparently because the origins of AD have not been identified. Invoking amyloid cascade, metal ions, and ROS production hypothesis of AD, herein we share our point of view on Cu(II) binding properties of A beta(4-x), the most prevalent N-truncated A beta peptide, currently known as the main constituent of amyloid plaques. The capability of A beta(4-x) to rapidly take over copper from previously tested A beta(1-x) peptides and form highly stable complexes, redox unreactive and resistant to copper exchange reactions, prompted us to propose physiological roles for these peptides. We discuss the new findings on the reactivity of Cu(II)A beta(4-x) with coexisting biomolecules in the context of synaptic cleft; we suggest that the role of A beta(4-x) peptides is to quench Cu(II) toxicity in the brain and maintain neurotransmission.