Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress

Curr Biol. 2005 Sep 6;15(17):1578-82. doi: 10.1016/j.cub.2005.07.036.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Dopamine / metabolism
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Hydrogen Peroxide / toxicity
  • Immunohistochemistry
  • Molecular Sequence Data
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics*
  • Paraquat / toxicity
  • Protein Deglycase DJ-1
  • Sequence Alignment


  • DJ-1alpha protein, Drosophila
  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Hydrogen Peroxide
  • DJ-1beta protein, Drosophila
  • Protein Deglycase DJ-1
  • Paraquat
  • Dopamine