| Project/Area Number |
10470157
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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 | The Institute of Physical and Chemical Research |
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Principal Investigator |
NUKINA Nobuyoshi MOLECULAR NEUROPATHOLOGY GROUP, The Institute of Physical and Chemical Research, GROUP DIRECTOR, 病因遺伝子研究グループ, グループディレクター(研究職) (10134595)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Yoshiro LAB. FOR CAG REPEAT DISEASES, The Institute of Physical and Chemical Research, CGAリピート病研究チーム, 研究員 (60211439)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | CAG repeat diseases / Polyglutamine / Intranuclear inclusion / Huntingtin / Huntington disease / CAGリピート |
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| Research Abstract |
1) Developing the cellular model and identification of binding protein
We have established an inducible cell system with ecdysone using neuro 2a cell line. The DNA introduced includes the exon 1 of huntingtin gene with 150, 60 and 20 CAG repeats with GFP. In this neuro 2a system, cell death occurred in neuro 2a with 150Q when it is differentiated and induced. We could observed cytoplasmic and nuclear aggregations which related to cell death. We are also analyzing the chaperones in this system and found HDJ2, HSP40, HSC70 and HSP70 are bound to the expanded polyglutamine. We are now looking for other proteins bound to polyglutamine.
2) Abnormal protein production in E.coli
We have established E.coli systems producing polyglutamine.
We have identified cell death in E.coli with expanded polyglutamine(pQ115). We analyzed this cell death system and found that DMSO and glycerol markedly decrease the cell death and the formation of insoluble aggregates.
3) The identification of nuclear transport factor
Nuclear transport related factors are also important which might relate to nuclear transport of polyglutamine. We have identified a new nuclear transport system in which RNA is involved. In yeast Mei2p, RNA-binding protein binds meiRNA and Mei2p was transported to nucleus, requiring meiRNA. The results open the possibilities that not only protein but also RNA might involve in the polyglutamine transport to the nucleus.
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