Pesticides directly accelerate the rate of α‐synuclein fibril formation: a possible factor in Parkinson's disease

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Abstract
Parkinson's disease involves intracellular deposits of α‐synuclein in the form of Lewy bodies and Lewy neurites. The etiology of the disease is unknown, however, several epidemiological studies have implicated environmental factors, especially pesticides. Here we show that several pesticides, including rotenone, dieldrin and paraquat, induce a conformational change in α‐synuclein and significantly accelerate the rate of formation of α‐synuclein fibrils in vitro. We propose that the relatively hydrophobic pesticides preferentially bind to a partially folded intermediate conformation of α‐synuclein, accounting for the observed conformational changes, and leading to association and subsequent fibrillation. These observations suggest one possible underlying molecular basis for Parkinson's disease.