Identification of cellulose ether susceptibility genes involved in suppression of prion disease development
| Project/Area Number |
19H03570
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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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| Review Section |
Basic Section 52020:Neurology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 遺伝子解析 / プロテオミクス解析 / プリオン / 防御機構 / セルロース誘導体 / 感受性 / gmfb / ゲノムマーカー |
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| Outline of Research at the Start |
本研究では、申請者がこれまで積み上げてきた独自の成果をさらに発展させる。すなわち、研究期間中に、日常摂取しているセルロース誘導体（ＣＥ）に応答してプリオンの増殖を長期間にわたり抑制するメカニズムに関わるＣＥ感受性遺伝子を同定する研究を行う。研究の成果はＣＥ効果の発現機序の解明に役立ち、これまで実体が捕らえられていなかったプリオンに対する生体防御機構の一端を解明することに繋がる。
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| Outline of Final Research Achievements |
In our bodies, it is thought that prion proliferation is controlled under the influence of some external factors, but the mechanism is unknown. The applicant has found that a cellulose derivative (CE), which is ingested daily as a food additive, exhibits excellent suppressive effect against prion disease for a long period of time. The CE effectiveness is clearly dependent on mouse strains. In the current study, genomic and proteomic analyses were performed between different CE-susceptible mice to search for host factors that affect CE-susceptibility. As a result, we finally identified polymorphisms in the gmfb gene and neighboring genes as genomic markers of CE-susceptibility. These findings are expected to lead to the elucidation of defense mechanisms against prions and the overcoming of prion diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
特発性プリオン病に罹患するのはごく少数の人だけであり、また同様にプリオンに曝露されても発病しない人たちがいることがわかっており、私たちの体内には何らかの外的要因等を受けプリオンの増殖を抑制する防御機構が備わっている。CE感受性はまさにそういった防御機構の一部となっている可能性があり、CE感受性と密接に結び付くゲノムマーカーを明らかにした本研究成果は、プリオンに対する防御機構の解明やプリオン病の克服に繋がる知見である。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.2020
Author(s)
Minikel EV, Zhao HT, Le J, O'Moore J, Pitstick R, Graffam S, Carlson GA, Kavanaugh MP, Kriz J, Kim JB, Ma J, Wille H, Aiken J, McKenzie D, Doh-ura K, Beck M, O'Keefe R, Stathopoulos J, Caron T, Schreiber SL, Carroll JB, Kordasiewicz HB, Cabin DE, Vallabh SM.
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Journal Title
Nucleic Acids Res.
Volume: 48(19)
Issue: 19
Pages: 10615-10631
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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