|Citation||Qurashi, A., Liu, H., Ray, L., Nelson, D.L., Duan, R., Jin, P. (2012). Chemical screen reveals small molecules suppressing fragile X premutation rCGG repeat-mediated neurodegeneration in Drosophila. Hum. Mol. Genet. 21(9): 2068--2075. (Export to RIS)|
|Publication Type||Research paper|
|PubMed Abstract||Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder recognized in fragile X premutation carriers. Using Drosophila, we previously identified elongated non-coding CGG repeats in FMR1 allele as the pathogenic cause of FXTAS. Here, we use this same FXTAS Drosophila model to conduct a chemical screen that reveals small molecules that can ameliorate the toxic effects of fragile X premutation ribo-CGG (rCGG) repeats, among them several known phospholipase A(2) (PLA(2)) inhibitors. We show that specific inhibition of PLA(2) activity could mitigate the neuronal deficits caused by fragile X premutation rCGG repeats, including lethality and locomotion deficits. Furthermore, through a genetic screen, we identified a PLA(2) Drosophila ortholog that specifically modulates rCGG repeat-mediated neuronal toxicity. Our results demonstrate the utility of Drosophila models for unbiased small molecule screens and point to PLA(2) as a possible therapeutic target to treat FXTAS.|
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|Language of Publication||English|
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|Abbreviation||Hum. Mol. Genet.|
|Title||Human Molecular Genetics|
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