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Drosophila Models of Proteinopathies: the Little Fly that Could

Author(s): , and Pedro Fernandez-Funez

Affiliation: Department of Neurology, 100 S. Newell Drive, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0236, USA.

Keywords: Drosophila models, neurodegeneration, protein misfolding, amyloids, Alzheimer, Parkinson, Huntington, Prion, proteinopathies, neurotoxicity

Abstract:

Alzheimer's, Parkinson's, and Huntington's disease are complex neurodegenerative conditions with high prevalence character-ized 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 neu-rodegenerative 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 molecu-lar and cellular perturbations caused by these proteins has not produced a single disease-modifying therapy. More than a decade ago, sev-eral groups demonstrated that human proteinopathies reproduce critical features of the disease in transgenic flies, including protein mis-folding, aggregation, and neurotoxicity. These in itial 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 envi-ronment, Drosophila models will need to expand their flexible, innovative, and multidisciplinary approaches to find new discoveries and translational applications.

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Article Details

VOLUME: 18
ISSUE: 8
Page: [1108 - 1122]
Pages: 15
DOI: 10.2174/138161212799315894