Parkinson's disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans

J Neural Transm (Vienna). 2010 May;117(5):599-604. doi: 10.1007/s00702-010-0397-4. Epub 2010 Apr 8.

Abstract

DJ-1 is a neuroprotective gene mutated in recessive Parkinson's disease (PD). In addition to direct protective functions in neurons, DJ-1 regulates neuroinflammatory signaling in primary mouse brain astrocytes. To assess the influence of DJ-1 on innate immunity signaling in vivo, we have generated djr-1 knockout Caenorhabditis elegans. When grown on pathogenic gram-negative bacteria, djr-1 (-/-) worms showed stronger phosphorylation of p38 mitogen-activated protein kinase (PMK-1) and hyper-induction of PMK-1 target genes. Thus, PD-associated DJ-1 contributes to regulation of innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Gene Expression Regulation / physiology
  • Gene Knockout Techniques
  • Immunity, Innate / genetics*
  • Mitogen-Activated Protein Kinases / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Parkinson Disease / genetics
  • Parkinson Disease / immunology
  • Parkinson Disease / metabolism
  • Phosphorylation / physiology
  • Signal Transduction / immunology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Nerve Tissue Proteins
  • Zebrafish Proteins
  • park7 protein, zebrafish
  • Mitogen-Activated Protein Kinases
  • Pmk-1 protein, C elegans