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

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Mathas, Nicolas | Poncet, Gabrielle | Laurent, Catherine | Larigot, Lucie | Le-Grand, Béatrice | Gonis, Elodie | Birman, Serge | Galardon, Erwan | Sari, Marie-Agnès | Tiouajni, Mounira | Nioche, Pierre | Barouki, Robert | Coumoul, Xavier | Mansuy, Daniel | Dairou, Julien

Edité par CCSD ; Elsevier -

International audience. 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.

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