Drosophila models of proteinopathies: The little fly that could

Diego E. Rincon-Limas, Kurt Jensen, Pedro Fernandez-Funez

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Alzheimer's, Parkinson's, and Huntington's disease are complex neurodegenerative conditions with high prevalence characterized by protein misfolding and deposition in the brain. Considerable progress has been made in the last two decades in identifying the genes and proteins responsible for several human 'proteinopathies'. A wide variety of wild type and mutant proteins associated with neurodegenerative conditions are structurally unstable, misfolded, and acquire conformations rich in ß-sheets (ß-state). These conformers form highly toxic self-assemblies that kill the neurons in stereotypical patterns. Unfortunately, the detailed understanding of the molecular and cellular perturbations caused by these proteins has not produced a single disease-modifying therapy. More than a decade ago, several groups demonstrated that human proteinopathies reproduce critical features of the disease in transgenic flies, including protein misfolding, aggregation, and neurotoxicity. These initial reports led to an explosion of research that has contributed to a better understanding of the molecular mechanisms regulating conformational dynamics and neurotoxic cascades. To remain relevant in this competitive environment, Drosophila models will need to expand their flexible, innovative, and multidisciplinary approaches to find new discoveries and translational applications.

Original languageEnglish (US)
Pages (from-to)1108-1122
Number of pages15
JournalCurrent pharmaceutical design
Volume18
Issue number8
DOIs
StatePublished - Mar 2012

Keywords

  • Alzheimer
  • Amyloids
  • Drosophila models
  • Huntington
  • Neurodegeneration
  • Parkinson
  • Prion
  • Protein misfolding

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