Neuro-epigenetics for the discover of novel pathomechanism of neurodegeneration.
Project/Area Number |
16H05319
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Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | The University of Tokyo |
Principal Investigator |
Iwata Atsushi 東京大学, 医学部附属病院, 准教授 (40401038)
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
Keywords | エピゲノム / アルツハイマー病 / ヒストン修飾 / 発現変化 / エピジェネティクス / 神経変性疾患 / レビー小体病 / KIi-ALS PD complex / BRCA1 / FGFR3 / 認知症 / メチル化 |
Outline of Final Research Achievements |
We challenged how we could use the diseased brain to extract information that might be specific and important to the disease. We performed indirect transcriptome analysis by purifying neuronal nuclei and extracting epigenome information from them as a methodology that enables resistance to postmortem changes and neural cell specific information extraction. By using this method, we were able to approach a new pathological condition of Alzheimer's disease. In other words, the function of DNA repair protein BRCA1 in nerve cells was reduced, which resulted in the reduction of nerve cell function. By applying this method, we performed neural cell-specific analysis of histone modification and found that expression changes of genes related to Alzheimer's disease are controlled by epigenetic.
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Academic Significance and Societal Importance of the Research Achievements |
全く新しい方法論を用いて剖検脳を用いることによって神経細胞内の遺伝子発現環境を推定,解析する方法論を確立し,それによる疾患特異的遺伝子発現異常を捉えることに成功した.これにより,アルツハイマー病の疾患発症メカニズムのより深い理解へとつながり,更には新規治療方法論の立案の一助となった.本本法論は,疾患脳発の情報抽出,すなわちボトムアップによる疾患理解という新しい疾患解析法となった.
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Report
(4 results)
Research Products
(18 results)