Abstract
Increased expression of Down Syndrome Cell Adhesion Molecule (Dscam) is implicated in the pathogenesis of brain disorders such as Down syndrome (DS) and fragile X syndrome (FXS). Here, we show that the cellular defects caused by dysregulated Dscam levels can be ameliorated by genetic and pharmacological inhibition of Abelson kinase (Abl) both in Dscam-overexpressing neurons and in a Drosophila model of fragile X syndrome. This study offers Abl as a potential therapeutic target for treating brain disorders associated with dysregulated Dscam expression.
Keywords:
Abl; D. melanogaster; Dscam; fragile X syndrome; neuronal development; neuroscience; presynaptic terminals; tyrosine kinase inhibitors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Cell Adhesion Molecules / genetics*
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Cell Adhesion Molecules / metabolism
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Disease Models, Animal
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Drosophila Proteins / genetics*
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Drosophila Proteins / metabolism
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Female
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Fragile X Syndrome / genetics*
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Fragile X Syndrome / metabolism
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Fragile X Syndrome / pathology
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Gene Expression Regulation
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Humans
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Male
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Neuronal Plasticity / genetics*
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Neurons / metabolism
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Neurons / pathology
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Neurons / ultrastructure
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / pathology
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Presynaptic Terminals / ultrastructure
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Protein Binding
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / genetics*
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Protein-Tyrosine Kinases / metabolism
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Signal Transduction
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Synapses / metabolism
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Synapses / pathology
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Synapses / ultrastructure
Substances
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Cell Adhesion Molecules
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Drosophila Proteins
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Dscam1 protein, Drosophila
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Protein-Tyrosine Kinases
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Abl protein, Drosophila