Drosophila Models of Proteinopathies: the Little Fly that Could
, and Pedro Fernandez-Funez
Pages 1108-1122 (15)
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.
Drosophila models, neurodegeneration, protein misfolding, amyloids, Alzheimer, Parkinson, Huntington, Prion, proteinopathies, neurotoxicity
Department of Neurology, 100 S. Newell Drive, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0236, USA.