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https://hdl.handle.net/2440/66685
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Type: | Journal article |
Title: | Perturbation of the Akt/Gsk3-beta signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs |
Author: | van Eyk, C. O'Keefe, L. Lawlor, K. Samaraweera, S. McLeod, C. Price, G. Venter, D. Richards, R. |
Citation: | Human Molecular Genetics, 2011; 20(14):2783-2794 |
Publisher: | Oxford Univ Press |
Issue Date: | 2011 |
ISSN: | 0964-6906 1460-2083 |
Statement of Responsibility: | Clare L. van Eyk, Louise V. O'Keefe, Kynan T. Lawlor, Saumya E. Samaraweera, Catherine J. McLeod, Gareth R. Price, Deon J. Venter and Robert I. Richards |
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. |
Keywords: | Animals Drosophila melanogaster Neurodegenerative Diseases Glycogen Synthase Kinase 3 Drosophila Proteins RNA Signal Transduction Gene Expression Repetitive Sequences, Nucleic Acid Proto-Oncogene Proteins c-akt Glycogen Synthase Kinase 3 beta |
Rights: | © The Author 2011. Copyright © 2011 Oxford University Press This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1093/hmg/ddr177 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/207830 http://purl.org/au-research/grants/nhmrc/453674 http://purl.org/au-research/grants/nhmrc/627183 |
Published version: | http://dx.doi.org/10.1093/hmg/ddr177 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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hdl_66685.pdf | Published version | 515.6 kB | Adobe PDF | View/Open |
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