Hyperoxia-induced neurodegeneration as a tool to identify neuroprotective genes in Drosophila melanogaster.
Oxidative stress has been reported to be a common underlying mechanism in the pathogenesis of many neurodegenerative disorders such as Alzheimer, Huntington, Creutzfeld-Jakob, and Parkinson disease. Despite the increasing number of articles showing a correlation between oxidative damage and neurodegeneration little is known about the genetic elements that confer protection against the deleterious effects of an oxidative imbalance in neurons. We show that oxygen-induced damage is a direct cause of brain degeneration in Drosophila and establish an experimental setup measuring dopaminergic neuron survival to model oxidative stress-induced neurodegeneration in flies. The overexpression of superoxide dismutase but not catalase was able to protect dopaminergic neurons against oxidative imbalance under hyperoxia treatment. In an effort to identify new genes involved in the process of oxidative stress-induced neurodegeneration, we have carried out a genome-wide expression analysis to identify genes whose expression is upregulated in fly heads under hyperoxia. Among them, a number of mitochondrial and cytoplasmic chaperones could be identified and were shown to protect dopaminergic neurons when overexpressed, thus validating our approach to identifying new genes involved in the neuronal defense mechanism against oxidative stress.
Institute of Zoology, University of Regensburg, Universitaetsstrasse 31, D-93040 Regensburg, Germany.
Christoph
C
Gruenewald
Jose A
JA
Botella
Florian
F
Bayersdorfer
Juan A
JA
Navarro
Stephan
S
Schneuwly
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D017344:Genes, Insect / Q000235:genetics*; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D018832:Molecular Chaperones; D018696:Neuroprotective Agents; D013482:Superoxide Dismutase; D010100:Oxygen