Transomics analysis of neuroimmune interaction in Parkinson's disease
| Project/Area Number |
17KT0130
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 特設分野 |
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| Research Field |
Complex Systems Disease Theory
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| Research Institution | Juntendo University |
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Principal Investigator |
Fukuhara Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (20359673)
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| Project Period (FY) |
2017-07-18 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | バイオマーカー / パーキンソン病 / 炎症性サイトカイン / トランスクリプトーム / オミクス解析 / 炎症 / トランスオミクス / CAGE解析 / 血液脳関門 / 血管内皮細胞 / 単球 |
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| Outline of Final Research Achievements |
To identify biomarker in the early stage of Parkinson’s disease, we employed transcriptome analysis for blood cells as well as iPS-derived neural lineage cells. Additionally, inflammatory cytokines and secreted molecules in blood plasma and serum were also examined as secretome analysis. Although transcriptome analysis identified temporal increase of THMD and AREG transcript, but sequential analysis in second year did not present these significant changes. Unlike blood transcriptome, cellular transcriptome during differentiation process indicated significant changes of MEG3 transcript, which is non-coding RNA was downregulated in entire lineage of PARK2 deficient background. PARK2 patients provided significant increase of IL-18 cytokine. In this study, we characterized dysregulation of PD at molecular level in both central nervous system and immune system, raising the further requirement of dictating missing link to reveal the underlying mechanism as well as therapeutic target.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はトランスオミクス的視座にたち、神経系細胞系譜の細胞と免疫系細胞との遺伝子ネットワークの共役性を明らかにしようとしたものである。PD患者の早期診断バイオマーカーは臨床的に早期の治療介入や疾患修飾療法の開発に重要であり、iPS細胞を利用したトランスクリプトーム解析ではメカニズムの一端を明らかにできたと考えられる。血中バイオマーカーについては既報との相違についてさらなる検証が必要と考えられるが、特にPARK2変異の遺伝的背景におけるメカニズムを説明しうる因子群が明らかとなったため、特に創薬標的候補を得る結果につながったと考えられる。
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Report
(3 results)
Research Products
(11 results)
