Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson's disease

Hum Mol Genet. 2003 Oct 1;12(19):2457-66. doi: 10.1093/hmg/ddg265. Epub 2003 Aug 5.


Transgenic Drosophila expressing human alpha-synuclein faithfully replicate essential features of human Parkinson's disease, including age-dependent loss of dopaminergic neurons, Lewy-body-like inclusions and locomotor impairment. To define the transcriptional program encoding molecular machinery involved in alpha-synuclein pathology, we characterized expression of the entire Drosophila genome at pre-symptomatic, early and advanced disease stages. Fifty-one signature transcripts, including lipid, energy and membrane transport mRNAs, were tightly associated with alpha-synuclein expression. Most importantly, at the pre-symptomatic stage, when the potential for neuroprotection is greatest, expression changes revealed specific pathology. In age-matched tau transgenic Drosophila, the transcription of alpha-synuclein associated genes was normal, suggesting highly distinct pathways of neurodegeneration. Temporal profiling of progressive gene expression changes in neurodegenerative disease models provides unbiased starting points for defining disease mechanisms and for identifying potential targets for neuroprotective drugs at pre-clinical stages.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal*
  • Drosophila*
  • Gene Expression Profiling
  • Gene Expression*
  • Genome
  • Humans
  • Lewy Bodies / pathology
  • Mutation
  • Nerve Degeneration / genetics*
  • Nerve Degeneration / pathology
  • Nerve Tissue Proteins / metabolism
  • Parkinson Disease / genetics*
  • Parkinson Disease / pathology
  • Polymerase Chain Reaction
  • Synucleins
  • Time Factors
  • Transcription, Genetic
  • Transgenes
  • alpha-Synuclein
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • tau Proteins