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.
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| http://dx.doi.org/10.7554/eLife.05196 | DOI Listing |
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Article Synopsis
- The study highlights the unique challenges in treating autism spectrum disorders (ASD) due to their diverse causes and emphasizes the need for individualized research approaches.
- Using human-induced pluripotent stem cell (iPSC) technology, researchers created neuron-like cells from an ASD patient with a mutation in the DSCAM gene, finding significant reductions in DSCAM levels and associated synaptic function genes.
- The findings indicate that the DSCAM mutation may lead to ASD symptoms by impairing NMDA receptor function, confirmed by observations in both iN cells and a mouse model with similar genetic alterations.
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