Coordination and redox properties of copper interaction with α-synuclein

Abstract

Parkinson's disease (PD) is a severe neurodegenerative disorder affecting movements. After Alzheimer's disease, it is the most common form of neurodegeneration. PD is characterized by the loss of neurons producing dopamine and by the presence of protein aggregates in the brain, known as Lewy bodies. The main constituent of Lewy bodies is the misfolded form of α-synuclein (αSyn), able to form oligomers and fibrils. In addition to protein aggregation, brain damage induced by oxidative stress, is also a frequent phenomenon in PD. αSyn is able to bind Copper ions in both Cu(II) and Cu(I) oxidation states. The metal binding is also maintained when αSyn interacts with membranes. Interestingly, copper binding to αSyn has strong impact either in protein misfolding or in free radical formation, such to provide a link between protein aggregation and oxidative damage. In this review the role of copper and αSyn in PD is discussed with a particular emphasis to elucidate (i) the interaction between copper and αSyn; (ii) the reactivity and (iii) potential toxicity associated with copper-αSyn complexes.

Keywords: Coordination sphere; Copper; Parkinson disease; Redox activity; Toxicity.