Copper(II) Binding to r-Synuclein, the Parkinson’s Protein

Parkinson’s disease is characterized by the accumulation of neuronal deposits comprising largely the protein R-synuclein (R-syn).1,2 Although rare heritable forms of the disease have been documented,3–6 the sporadic form is far more common and possibly connected to environmental factors that promote oxidative stress and aberrant metal-mediated redox chemistry.7–12 Indeed, metal-enhanced oligomerization has been observed for R-syn in vitro,13,14 and there is evidence that specific metal-protein interactions are critical in neurodegenerative diseases involving other amyloidogenic polypeptides such as amyloid peptide (Alzheimer’s disease),15–17 prion protein (spongiform encephalopathies),18,19 and superoxide dismutase (amyotrophic lateral sclerosis).20,21 A difficult issue to resolve is whether metal ions perturb protein structures and thereby alter function, whether metal-protein complexes directly participate in the production of reactive oxygen species, or whether bot