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Perturbation of the Akt/Gsk3-ß signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.

Journal Article


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.

UOW Authors


  •   Venter, Deon (external author)

Publication Date


  • 2011

Citation


  • van Eyk, C. L., O'Keefe, L. V., Lawlor, K. T., Samaraweera, S. E., McLeod, C. J., Price, G. R., . . . Richards, R. I. (2011). Perturbation of the Akt/Gsk3-ß signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.. Human molecular genetics, 20(14), 2783-2794. doi:10.1093/hmg/ddr177

Web Of Science Accession Number


Start Page


  • 2783

End Page


  • 2794

Volume


  • 20

Issue


  • 14

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.

UOW Authors


  •   Venter, Deon (external author)

Publication Date


  • 2011

Citation


  • van Eyk, C. L., O'Keefe, L. V., Lawlor, K. T., Samaraweera, S. E., McLeod, C. J., Price, G. R., . . . Richards, R. I. (2011). Perturbation of the Akt/Gsk3-ß signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.. Human molecular genetics, 20(14), 2783-2794. doi:10.1093/hmg/ddr177

Web Of Science Accession Number


Start Page


  • 2783

End Page


  • 2794

Volume


  • 20

Issue


  • 14