Basic Research for Development of Novel Therapeutics of Polyglutamine Diseases through Transcriptional Regulation
| Project/Area Number |
16390249
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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 | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
OKAZAWA Hitoshi TOKYO MEDICAL AND DENTAL UNIVERSITY, Medical Research Institute, Professor, 難治疾患研究所, 教授 (50261996)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | transcription / neuron / polyglutamine / cell death / hsp70 / proteome / transcriptome / neurodegeneration / 転写障害 / PQBP1 / Hsp70 / ペプチド / BrU |
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| Research Abstract |
In this study, we investigated changes of gene expression profiles by transcriptome and proteome analyses. We have found multiple candidate genes whose expression changes in specific types of neurons affected in polyQ diseases. Among them, we currently focus on hsp70 whose expression was dramatically up-regulated instriatal neurons by mutant huntingtin expression but not by mutant ataxin-1. The remarkable increase was not observed in other types of neurons such as granule cells or cortical neurons. We further analyzed molecular mechanisms underlying transcriptional upregulation, and found that HSF1, a famous transcription factor affecting expression of heat shock proteins, is not involve in the upregulation by mutant htt. Instead, we found another transcription factor p53 is critically involved in the regulation of hsp70 expression.
We plan to use the result for developing nove therapeutics in the future.
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Report
(3 results)
Research Products
(13 results)
