title: Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress.
abstract: The loss of dopaminergic neurons in the substantia nigra is the pathological hallmark of Parkinson's disease (PD). While the etiology of sporadic PD remains elusive, an inherited form of early-onset familial PD is linked to mutations of DJ-1. To understand the biological function of DJ-1 and its relevance to the pathogenesis of PD, we investigated the function of DJ-1 using Drosophila. Drosophila possesses two homologs of human DJ-1: DJ-1alpha and DJ-1beta. We found that DJ-1alpha is expressed predominantly in the testis, while DJ-1beta is ubiquitously present in most tissues, resembling the expression pattern of human DJ-1. Loss-of-function DJ-1beta mutants demonstrated an extended survival of dopaminergic neurons and resistance to paraquat stress, but showed acute sensitivity to hydrogen peroxide treatment. We showed a compensatory upregulation of DJ-1alpha expression in the brain of the DJ-1beta mutant and demonstrated that overexpression of DJ-1alpha in dopaminergic neurons is sufficient to confer protection against paraquat insult. These results suggest that Drosophila homologs of DJ-1 play critical roles in the survival of dopaminergic neurons and response to oxidative stress.
authors.affiliation: Neurogenetics Branch MSC 3705, Building 35, Room 2A 1002 NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Menzies
authors.forename: Sarat C
authors.initials: SC
authors.lastname: Yenisetti
authors.forename: Kyung-Tai
authors.initials: KT
authors.lastname: Min
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010269:Paraquat / Q000633:toxicity; D000071617:Protein Deglycase DJ-1; D016415:Sequence Alignment
chemical_list: C506878:DJ-1alpha protein, Drosophila; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D006861:Hydrogen Peroxide; C506879:DJ-1beta protein, Drosophila; D000071617:Protein Deglycase DJ-1; D010269:Paraquat; D004298:Dopamine