Inhibition by pesticides of the DJ-1/Park7 protein related to Parkinson disease.

Parkinson's disease is a severe neurodegenerative disease. Several environmental contaminants such as pesticides have been suspected to favor the appearance of this pathology. The protein DJ-1 (or Park7) protects against the development of Parkinson's disease. Thus, the possible inhibitory effects of about a hundred pesticides on human DJ-1 have been studied. We identified fifteen of them as strong inhibitors of DJ-1 with IC50 values between 0.02 and 30 µM. Thiocarbamates are particularly good inhibitors, as shown by thiram that acts as an irreversible inhibitor of an esterase activity of DJ-1 with an IC50 value of 0.02 µM. Thiram was also found as a good inhibitor of the protective activity of DJ-1 against glycation. Such inhibitory effects could be one of the various biological effects of these pesticides that may explain their involvement in the development of Parkinson's disease.