Analysis of gene expression changes in a cellular model of Parkinson disease

Neurobiol Dis. 2005 Feb;18(1):54-74. doi: 10.1016/j.nbd.2004.08.016.

Abstract

We employed Serial Analysis of Gene Expression to identify transcriptional changes in a cellular model of Parkinson Disease (PD). The model consisted of neuronally differentiated PC12 cells compared before and after 8 hours' exposure to 6-hydroxydopamine. Approximately 1200 transcripts were significantly induced by 6-OHDA and approximately 500 of these are currently matched to known genes. Here, we categorize the regulated genes according to known functional activities and discuss their potential roles in neuron death and survival and in PD. We find induction of multiple death-associated genes as well as many with the capacity for neuroprotection. This suggests that survival or death of individual neurons in PD may reflect an integrated response to both protective and destructive gene changes. Our findings identify a number of regulated genes as candidates for involvement in PD and therefore as potential targets for therapeutic intervention. Such intervention may include both inhibiting the induction/activity of death-promoting genes and enhancing those with neuroprotective activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Death / genetics
  • Cell Differentiation / drug effects
  • Cell Survival / genetics
  • Dopamine / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics*
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / genetics*
  • Nerve Degeneration / metabolism
  • Nerve Growth Factor / pharmacology
  • Nerve Tissue Proteins / genetics
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidative Stress / genetics
  • Oxidopamine
  • PC12 Cells
  • Parkinson Disease / genetics*
  • Protein Folding
  • Rats
  • Transcription Factors / genetics

Substances

  • Nerve Tissue Proteins
  • Transcription Factors
  • Oxidopamine
  • Nerve Growth Factor
  • Dopamine