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- W2912659015 abstract "Expansion of CAG repeat coding polyglutamine (polyQ) stretch causes neurodegenerative diseases such as Huntington Disease (HD) and several types of spinocerebellar ataxia (SCA). The proteins harboring polyQ expansion misfold and form intranuclear inclusions. Drosophila models of various polyQ diseases have been established by expressing disease proteins harboring polyQ expansion in neurons, and they show aggregation formation in nucleus, locomotor defects, and premature death. Transcriptional dysregulation may be involved in the pathogenesis of polyQ diseases. In previous study, we reported that expression of polyQ peptides without protein context except for short peptides (polyQ108myc/flag) in neurons attenuated CREB activity in Drosophila. Here, we demonstrate that protein contexts harboring polyQ stretch play important roles on CREB activity. We tested two disease proteins, Huntingtin and SCA3, which are causative for HD or SCA type3, respectively. Truncated Huntingtin (Htt) protein and full length or truncated SCA3 protein with normal or toxic range of length of polyQ are expressed in neurons with Gal4/UAS system, and CREB activity was measured by in vivo reporter. We found that CREB activity was decreased in the flies that are overexpressed Htt with expanded polyQ (HttpolyQ128) in neurons, although expression of Htt without polyQ (HttQ0) rather increased CREB activity. In contrast, expression of SCA3–Q84 did not dampen CREB activity. Truncated SCA–3 protein with polyQ expansion fused to nuclear localization signal (SCA3–Q68 NLS) attenuated CREB activity, but that with nuclear export signal (SCA3–Q77 NES) did not. These results suggest that the molecular mechanisms underlying pathogenesis of polyQ diseases are specific to protein context." @default.
- W2912659015 created "2019-02-21" @default.
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- W2912659015 date "2006-07-01" @default.
- W2912659015 modified "2023-09-27" @default.
- W2912659015 title "P1-398: Characterization of the effect of protein contexts harboring polyglutamine stretch on CREB activity in Drosophila" @default.
- W2912659015 doi "https://doi.org/10.1016/j.jalz.2006.05.776" @default.
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