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Journal Articles Toxicology Year : 2023

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

Abstract

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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Dates and versions

hal-04230908 , version 2 (09-10-2023)
hal-04230908 , version 1 (27-11-2023)

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Nicolas Mathas, Gabrielle Poncet, Catherine Laurent, Lucie Larigot, Béatrice Le-Grand, et al.. Inhibition by pesticides of the DJ-1/Park7 protein related to Parkinson disease.. Toxicology, 2023, 487, pp.153467. ⟨10.1016/j.tox.2023.153467⟩. ⟨hal-04230908v2⟩
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