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Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models.
Trends in Neurosciences 2018 July
GGGGCC (G4 C2 ) repeat expansion in C9ORF72 is the most common genetic cause of ALS and FTD. An important issue is how repeat RNAs and their translation products, various dipeptide repeat (DPR) proteins, cause neurodegeneration. Drosophila has been widely used to model G4 C2 repeat RNA and DPR protein toxicity. Overexpression of disease molecules in flies has revealed important molecular insights. These have been validated and further explored in human neurons differentiated from induced pluripotent stem cells (iPSCs), a disease-relevant model in which expanded G4 C2 repeats are expressed in their native molecular context. Approaches that combine the genetic power of Drosophila and the disease relevance of iPSC-derived patient neurons will continue to unravel the underlying pathogenic mechanisms and help identify potential therapeutic targets in C9ORF72-ALS/FTD.
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