DJ-1 as a modulator of autophagy: an hypothesis.
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.
González-Polo
Rosa A
RA
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Departamento de Bioquímica y Biología Molecular y Genética, E.U. Enfermería y T.O., Universidad de Extremadura, Cáceres, Spain. rosapolo@unex.es
Niso-Santano
Mireia
M
Gómez-Sánchez
Rubén
R
Bravo-San Pedro
José M
JM
Fuentes
José M
JM
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006540:Herbicides / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010269:Paraquat / Q000494:pharmacology; D000071617:Protein Deglycase DJ-1; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism
D006540:Herbicides; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; C025946:3-methyladenine; D045304:Cytochromes c; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D053148:Caspase 3; D000225:Adenine; D010269:Paraquat