TY - JOUR
T1 - Drosophila models of proteinopathies
T2 - The little fly that could
AU - Rincon-Limas, Diego E.
AU - Jensen, Kurt
AU - Fernandez-Funez, Pedro
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Alzheimer
KW - Amyloids
KW - Drosophila models
KW - Huntington
KW - Neurodegeneration
KW - Parkinson
KW - Prion
KW - Protein misfolding
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U2 - 10.2174/138161212799315894
DO - 10.2174/138161212799315894
M3 - Article
C2 - 22288402
AN - SCOPUS:84857135997
SN - 1381-6128
VL - 18
SP - 1108
EP - 1122
JO - Current pharmaceutical design
JF - Current pharmaceutical design
IS - 8
ER -