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, Alzheimer's 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 Aβ4-x, the most prevalent N-truncated Aβ peptide, currently known as the main constituent of amyloid plaques. The capability of Aβ4-x to rapidly take over copper from previously tested Aβ1-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)Aβ4-x with coexisting biomolecules in the context of synaptic cleft; we suggest that the role of Aβ4-x peptides is to quench Cu(II) toxicity in the brain and maintain neurotransmission.