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Volume 10, Pages 1574-1579
Directions in Science

DJ-1 as a Modulator of Autophagy: An Hypothesis

Centro de Investigacion Biomedica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Bioquímica y Biología Molecular y Genética, E.U. Enfermería y T.O., Universidad de Extremadura, Cáceres, Spain

Received 5 March 2010; Revised 23 July 2010; Accepted 24 July 2010

Academic Editor: George Siegel

Copyright © 2010 Rosa A. González-Polo et al.


The etiology of Parkinson's disease (PD) is not completely defined, although environmental factors (for example, exposure to the herbicide paraquat [PQ]) and genetic susceptibility (such as DJ-1 mutations that have been associated with an autosomal-recessive form of early-onset PD) have been demonstrated to contribute. Alterations in macroautophagy have been described in the pathogenesis of this neurodegenerative disease. We have established a model system to study the involvement of the DJ-1 protein in PQ-induced autophagy. When we transfected cells exposed to PQ with DJ-1–specific siRNA, we observed an inhibition of the autophagic events induced by the herbicide, as well as sensitization additive with PQ-induced apoptotic cell death and exacerbation of this cell death in the presence of the autophagy inhibitor 3-methyladenine. These results suggest, for the first time, an active role for DJ-1 in the autophagic response produced by PQ, opening the door to new strategies for PD therapy.