Transcriptional disturbance and Neurodegeneration.
| Project/Area Number |
15390272
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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) |
IGARASHI Shuichi Niigata University, Medical and Dental Hospital, Lecture, 医歯学総合病院, 講師 (60345519)
OYAKE Mutsuo Niigata University, Medical and Dental Hospital, Assistant, 医歯学総合病院, 助手 (70313559)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2003: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | polyglutamine / spinocerebellar ataxia / CREB mediated transcription / UPS / APTX / DNA repair / XRCC1 / poly(ADP-ribose)polymerase |
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| Research Abstract |
By using isogenic stable inducible cell lines, we showed the polyglutamine stretch suppressed the CRE dependent transcription in their early stage. However their repressive effects were not so dramatically different in different cell lines which have different length of polyglutamine stretch. Furthermore its repressive effect is not affected the existence of aggregate formation. Taken together CRE mediated transcriptional repression was not a pathogenic for polyglutamine disease. By using these cell lines, we showed the expanded polyglutamine stretch retained in cell, speciously in nucleus by length dependent manner. The UPS, one of the main systems to degradate unfolded proteins in cells, was not suppressed in these cell lines. Therefore we speculated that polyglutamine stretch itself has resistance to degradation, thus accumulate in nucleus.
The other neurodegenerative disorders, early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH/AOA1) is caused by mutation of APTX. We show the APTX binds to X-ray repair cross-complementing group 1 protein, which is the scaffold protein for base excision repair (BER) machinery in single strand DNA break repair (SSBR), and made complex with poly (ADP-ribose) polymerase. These findings support the idea that APTX might take an important role in SSBR system.
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Report
(3 results)
Research Products
(33 results)
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[Journal Article] Beta-synuclein gene alterations in dementia with Lewy bodies.2004
Author(s)
Ohtake H, Limprasert P, Fan Y, Onodera O, Kakita A, Takahashi H, Bonner LT, Tsuang DW, Murray IV, Lee VM, Trojanowski JQ, Ishikawa A, Idezuka J, Murata M, Toda T, Bird TD, Leverenz JB, Tsuji S, La Spada AR.
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Journal Title
Neurology. 63(5)
Pages: 805-811
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Aprataxin, a novel protein that protects against genotoxic stress.2004
Author(s)
Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF.
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Journal Title
Hum Mol Genet. Epub 2004 Mar 25 13(10)
Pages: 1081-1093
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein.2004
Author(s)
Sano Y, Date H, Igarashi S, Onodera O, Oyake M, Takahashi T, Hayashi S, Morimatsu M, Takahashi H, Makifuchi T, Fukuhara N, Tsuji S.
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Journal Title
Ann Neurol. 55(2)
Pages: 241-249
Description
「研究成果報告書概要(欧文)」より
Related Report
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