Reference Report

Reference
Citation	Chang, S., Bray, S.M., Li, Z., Zarnescu, D.C., He, C., Jin, P., Warren, S.T. (2008). Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat. Chem. Biol. 4(4): 256--263. (Export to RIS)
FlyBase ID	FBrf0204377
Publication Type	Research paper
PubMed ID	18327252
PubMed Abstract	Fragile X syndrome is caused by the functional loss of the fragile X mental retardation 1 (FMR1) gene. Deletion of the FMR1 ortholog in Drosophila melanogaster (Fmr1) recapitulates many phenotypes associated with fragile X syndrome. We have discovered that Fmr1 mutant Drosophila die during development when reared on food containing increased levels of glutamate, which is consistent with the theory that FMR1 loss results in excess glutamate signaling. Using this lethal phenotype, we screened a chemical library of 2,000 compounds and identified nine molecules that rescued the lethality, including three that implicate the GABAergic inhibitory pathway. Indeed, GABA treatment rescued several known Fmr1 mutant phenotypes in flies, including mushroom bodies defects, excess Futsch translation and abnormal male courtship behavior. These data are consistent with GABAergic inhibition of the enhanced excitatory pathway in fragile X syndrome. In addition, our screen reveals that the muscarinic cholinergic receptors may have a role in fragile X syndrome in parallel to the GABAergic pathway. These results point to potential therapeutic approaches for treating fragile X syndrome.
DOI	10.1038/nchembio.78
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nat. Chem. Biol.
Title	Nature Chemical Biology
Publication Year	2005-
ISBN/ISSN	1552-4450 1552-4469
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Genes (2)
	Fmr1 futsch