Abstract
Parkinson's disease is a neurodegenerative disorder associated with oxidative stress and the death of melanin-containing neurons of the substantia nigra. Epidemiological evidence links exposure to the pesticide paraquat (PQ) to Parkinson's disease, and this link has been explained by a redox cycling mechanism that induces oxidative stress. Here, we used a novel electrochemistry-based reverse engineering methodology to test the hypothesis that PQ can undergo reductive redox cycling with melanin. In this method, (i) an insoluble natural melanin (from Sepia melanin) and a synthetic model melanin (having a cysteinyldopamine-melanin core and dopamine-melanin shell) were entrapped in a nonconducting hydrogel film adjacent to an electrode, (ii) the film-coated electrode was immersed in solutions containing PQ (putative redox cycling reductant) and a redox cycling oxidant (ferrocene dimethanol), (iii) sequences of input potentials (i.e., voltages) were imposed to the underlying electrode to systematically engage reductive and oxidative redox cycling, and (iv) output response currents were analyzed for signatures of redox cycling. The response characteristics of the PQ-melanin systems to various input potential sequences support the hypothesis that PQ can directly donate electrons to melanin. This observation of PQ-melanin redox interactions demonstrates an association between two components that have been individually linked to oxidative stress and Parkinson's disease. Potentially, melanin's redox activity could be an important component in understanding the etiology of neurological disorders such as Parkinson's disease.
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