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.
Keywords: Drosophila models, neurodegeneration, protein misfolding, amyloids, Alzheimer, Parkinson, Huntington, Prion, proteinopathies, neurotoxicity
Current Pharmaceutical Design
Title: Drosophila Models of Proteinopathies: the Little Fly that Could
Volume: 18 Issue: 8
Author(s): Diego E. Rincon-Limas, Kurt Jensen and Pedro Fernandez-Funez*
Affiliation:
- Department of Neurology, 100 S. Newell Drive, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0236,United States
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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Cite this article as:
Rincon-Limas Diego E. , Jensen Kurt and Fernandez-Funez Pedro*, Drosophila Models of Proteinopathies: the Little Fly that Could, Current Pharmaceutical Design 2012; 18 (8) . https://dx.doi.org/10.2174/138161212799315894
DOI https://dx.doi.org/10.2174/138161212799315894 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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