Knocking out DJ-1 attenuates astrocytes neuroprotection against 6-hydroxydopamine toxicity

J Mol Neurosci. 2013 Jul;50(3):542-50. doi: 10.1007/s12031-013-9984-9. Epub 2013 Mar 28.


Astrocytes are the most abundant glial cell type in the brain. Impairment in astrocyte functions can critically influence neuronal survival and leads to neurodegeneration. Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by motor dysfunction that results from progressive neuronal loss. Astrocytic dysfunction was demonstrated in human samples and in experimental models of PD. Mutations in DJ-1 (PARK7) leading to loss of functional protein cause familial PD and enhance sensitivity to oxidative insults. Recently, an increase in DJ-1's expression was found in reactive astrocytes in various neurodegenerative disorders. Here we show that lack of DJ-1 attenuates astrocytes' ability to support neuronal cells, thereby leading to accelerated neuronal damage. DJ-1 knockout mice demonstrated increased vulnerability in vivo to 6-hydroxydopamine (6-OHDA) hemiparkinsonian PD model. Astrocytes isolated from DJ-1 knockout mice showed an inferior ability to protect human neuroblastoma cells against 6-OHDA insult both by co-culture and through their conditioned media, as compared to wild-type astrocytes. DJ-1 knockout astrocytes showed blunted ability to increase the expression of cellular protective mechanisms against oxidative stress mediated via Nrf-2 and HO-1 in response to exposure to 6-OHDA. These experiments demonstrated that lack of DJ-1 impairs astrocyte-mediated neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Culture Media, Conditioned / pharmacology
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / metabolism
  • Neurons / drug effects
  • Neurons / pathology
  • Oncogene Proteins / genetics*
  • Oxidative Stress
  • Oxidopamine / toxicity
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Peroxiredoxins
  • Protein Deglycase DJ-1


  • Culture Media, Conditioned
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Oncogene Proteins
  • Oxidopamine
  • Peroxiredoxins
  • Heme Oxygenase-1
  • PARK7 protein, mouse
  • Protein Deglycase DJ-1