The many faces of α-Synuclein and copper: A “complex” relationship

Parkinson disease (PD) belongs to a group of neurodegenerative disorders collectively known as Synucleinopathies, characterized pathologically by the presence of neuronal or oligodendrocyte inclusions, or both, composed of aggregated alpha-synuclein (aS). Transition metal ion homeostasis (copper, iron, zinc) plays an important role in neurodegenerative disorders, with protein–metal interactions be a potential link between the pathological processes of protein aggregation, oxidative damage and neuronal cell death. From the different metal ions studied in the metallochemistry of aS, the role of copper ions in aS function and dysfunction became a central question in the pathophysiology of PD. . Our studies indicate that the formation of copper-aS complex(es) might have physiologically and pathological implications, revealing a “complex” relationship between the protein and the metal ion. Overall, our findings open new avenues of investigations into the metallobiology of PD, reshaping the consideration of copper mediated aS pathology in vivo.