Crossroads between copper ions and amyloid formation in Parkinson's disease.

Abstract

Copper (Cu) ion dys-homeostasis and α-synclein amyloid deposits are two hallmarks of Parkinson's disease (PD). Here, I will discuss the connections between these features, with a major focus on the role of Cu in the α-synuclein (aS) amyloid formation process. The structurally disordered aS monomer can bind to both redox states of Cu (i.e., oxidized Cu(II) and reduced Cu(I)) with high affinity in vitro. Notably, the presence of Cu(II) (in absence of aS N-terminal acetylation) and Cu(I) (when in complex with the copper chaperone Atox1) modulate aS assembly into β-structured amyloids in opposite directions in vitro. Albeit the link to biological relevance is not fully unraveled, existing observations clearly emphasize the need for more knowledge on this interplay and its consequences to eventually combat destructive reactions that promote PD.