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Unraveling the Basis of Neurodegeneration using the Drosophila Eye

  • Pedro Fernandez-Funez
  • Jonatan Sanchez-Garcia
  • Diego E. Rincon-Limas
Chapter

Abstract

Research progress over the last 20 years has identified misfolded proteins and RNAs bearing noncoding repeat expansions as the culprits in most neurodegenerative diseases. This is the diverse group of brain disorders that typically strikes in mid-to-late life causing progressive loss of motor and/or cognitive functions. Pathologically, these diseases are characterized by the aberrant accumulation of protein (amyloids) and RNA (nuclear foci) in brain neurons. It is unclear, though, how these pathogenic assemblies ultimately cause cell death. To fill this gap, these rogue proteins and RNAs have been expressed in transgenic animal models, including the little fly Drosophila melanogaster. In most cases, these neurotoxic agents preserved their intrinsic pathogenicity, resulting in relevant models to understand how they induce neuronal loss. In this regard, the fly eye has become an invaluable research tool because (i) the precise arrangement of its 800 ommatidia facilitates the detection of structural perturbations and (ii) the eye, unlike the brain, is not required for viability. In addition, the unmatched arsenal of genetic tools enables the validation of candidate genes as well as the discovery of unsuspected molecular mechanisms through genetic interactions. Moreover, the recent combination of in silico and in vitro screens followed by validation in the fly eye has provided a wealth of new targets with potential therapeutic application. This chapter describes the Drosophila eye as a powerful tool in the identification of the genetic mechanisms associated with neurodegenerative processes and the discovery of neuroprotective drugs.

Keywords

Amyotrophic Lateral Sclerosis Ataxia Telangiectasia Mutate Myotonic Dystrophy polyQ Disease polyQ Expansion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank the Bloomington Drosophila Stock Center for strains. We want to apologize for those whose work we could not cite due to space constraints. This work was supported by the NIH grants DP2OD002721 to PF-F and R21NS081356 to DER-L, and star-up funding from the Department of Neurology (UF) to PF-F and DER-L.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Pedro Fernandez-Funez
    • 1
    • 2
    • 3
    • 4
  • Jonatan Sanchez-Garcia
    • 1
  • Diego E. Rincon-Limas
    • 1
    • 3
    • 4
  1. 1.Department of Neurology, McKnight Brain InstituteUniversity of FloridaGainesvilleUSA
  2. 2.Department of NeurosciencesUniversity of FloridaGainesvilleUSA
  3. 3.Department of Neuroscience, Genetics Institute and Center for Translational Research on Neurodegenerative DiseasesUniversity of FloridaGainesvilleUSA
  4. 4.Center for Movement Disorders and NeurorestorationUniversity of FloridaGainesvilleUSA

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