title: Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.
abstract: Recent evidence supports a role for RNA as a common pathogenic agent in both the 'polyglutamine' and 'untranslated' dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin-forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcript levels as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease-associated repeat sequences--CAG, CUG and AUUCU--were specifically expressed in the neurons of Drosophila and resultant common transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3-β signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.
authors.affiliation: Discipline of Genetics, School of Molecular and Biomedical Sciences and ARC Special Research Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: van Eyk
authors.forename: Louise V
authors.initials: LV
authors.lastname: O'Keefe
authors.forename: Kynan T
authors.initials: KT
authors.lastname: Lawlor
authors.forename: Saumya E
authors.initials: SE
authors.lastname: Samaraweera
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: McLeod
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Price
authors.forename: Deon J
authors.initials: DJ
authors.lastname: Venter
authors.forename: Robert I
authors.initials: RI
authors.lastname: Richards
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D012313:RNA; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3