Abstract
Transcriptional dysregulation as a result of sequestration of essential transcription factors into protein aggregates formed by polyglutamine (polyQ) expansions can lead to late-onset progressive neurodegeneration. DNA microarray analysis of Drosophila expressing polyQ in the compound eye over time revealed large numbers of transcriptional changes at the earliest stages of the disease including repression of the transient receptor potential calcium channels in a polyQ-induced cell death specific manner. While significant differences in expression profiles were found between the Drosophila compound eye and polyQ-sensitive neural cells, a number of possible key overlapping regulators were extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity, suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.
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Abbreviations
- polyQ:
-
polyglutamine
- Htt:
-
Huntingtins
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Acknowledgements
We are grateful to T Nishimura, P Jorgensen, and G Cagney for comments on the manuscript, N Itoh for technical assistance and to the Bloomington Stock Center for fly stocks. We are also grateful to N Nukina, S Nagata, T Igaki, N Bonini, J Chung and G Thomas for materials. This work was supported in part by grants from the Japanese Ministry of Education, Science, Sports, Culture and Technology to MM, HN and SN. This work was also supported in part by a RIKEN Bioarchitect Research Grant to MM. HK is a research fellow of the Special Postdoctoral Researchers Program, RIKEN.
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Nelson, B., Nishimura, S., Kanuka, H. et al. Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration. Cell Death Differ 12, 1115–1123 (2005). https://doi.org/10.1038/sj.cdd.4401635
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DOI: https://doi.org/10.1038/sj.cdd.4401635
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