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

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

doi:10.1016/j.tox.2023.153467

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

Toxicology. 2023 Mar 15:487:153467. doi: 10.1016/j.tox.2023.153467. Epub 2023 Feb 24.

Authors

Affiliations

¹ Université Paris cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints Pères, F-75006 Paris, France.
² Université Paris Cité, 45 rue des Saints Pères, F-75006 Paris, France; INSERM, UMR-S1124, T3S, 45 rue des Saints Pères, F-75006 Paris, France.
³ Université Paris cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints Pères, F-75006 Paris, France; Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France.
⁴ Genes Circuits Rhythms and Neuropathology, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France.
⁵ Université Paris Cité, 45 rue des Saints Pères, F-75006 Paris, France; INSERM, UMR-S1124, T3S, 45 rue des Saints Pères, F-75006 Paris, France; Structural and Molecular Analysis Platform, BioMedTech Facilities INSERM US36-CNRS UMS2009, Université Paris Cité, Paris, France.
⁶ Université Paris cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, 45 rue des Saints Pères, F-75006 Paris, France. Electronic address: julien.dairou@u-paris.fr.

PMID: 36842454
DOI: 10.1016/j.tox.2023.153467

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.

Keywords: Neurodegenerative diseases; Park7; Pesticides; Thiocarbamates.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neurodegenerative Diseases*
Parkinson Disease* / pathology
Pesticides* / toxicity
Protein Deglycase DJ-1 / genetics
Protein Deglycase DJ-1 / metabolism
Thiram

Substances

Pesticides
Protein Deglycase DJ-1
Thiram
PARK7 protein, human