Research for the role of dystrophic neurites in neuronal cell dysfunction of Polyglutamine disease
| Project/Area Number |
13670635
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
ONODERA Osamu Niigata University Brain research institute, Associate professor, 脳研究所, 助教授 (20303167)
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| Co-Investigator(Kenkyū-buntansha) |
OYAKE Mutsuo University Medical Hospital, Assistant, 医学部附属病院, 助手 (70313559)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | polyglutamine / Huntington disease / DRPLA / unfolding protein / MTOC / aggresome / intermediate filaments / microtubules filaments / polygultamine / huntington disease |
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| Research Abstract |
To understand the pathogenetic mechanisms underlying polyglutamine diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA).
We demonstrated that the expression of a truncated DRPLA protein containing expanded polyQ stretches in COS-7 cells resulted in the formation of perinuclear aggregate bodies that are co-localized with γ-tubulin, a protein marker for the microtubules-organizing center (MTOC). A collapsed vimentin network surrounded these aggregate bodies. Furthermore, disruption of the microtubules with nocodazole resulted in the formation of small aggregate bodies that were scattered throughout the cytoplasm. These findings suggest that the truncated DRPLA proteins containing expanded polyQ stretches unfold and form small aggregate bodies in the cell periphery. These aggregates move on microtubules to the MTOC, where they remain as distinct "aggresomes".
Then we have established several stable cell lines, which expressed polyQ stretches under control of tetracycline. In these cell lines, the integration sites are identical so we could exclude the effect of a chromosomal localization of integrated cDNA. Using these stable cell lines we have seen the turnover rates of polyQ stretch is different.
In future we will analysis the effects of the difference of the fate of polyQ stretch by their length on neuronal cell function, specially their axonal transport system.
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Report
(3 results)
Research Products
(19 results)
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[Publications] Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, Koike R, Hiroi T, Yuasa T, Awaya Y, Sakai T, Takahashi T, Nagatomo H, Sekijima Y, Kawachi I, Takiyama Y, Nishizawa M, Fukuhara N, Saito K, Sugano S, Tsuji S: "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene"Nat Genet. 29(2). 184-188 (2001)
Description
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