| Project/Area Number |
18KT0027
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
Saiki Shinji 順天堂大学, 医学部, 准教授 (00339996)
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| Co-Investigator(Kenkyū-buntansha) |
笹澤 有紀子 順天堂大学, 医学(系)研究科(研究院), 特任助教 (20594922)
赤松 和土 順天堂大学, 医学(系)研究科(研究院), 教授 (60338184)
舩山 学 順天堂大学, 医学部, 准教授 (70468578)
石川 景一 順天堂大学, 医学(系)研究科(研究院), 助教 (90733973)
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| Project Period (FY) |
2018-07-18 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | パーキンソン病 / バイオマーカー / オートファジー / ポリアミン / ジアセチルスペルミジン / スペルミン / スペルミジン / miRNA / 遠隔効果 / 神経変性疾患 |
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| Outline of Final Research Achievements |
We evaluated the ability of each polyamine metabolite to act as age-related, diagnostic and severity-associated PD biomarkers. Comprehensive metabolome analysis of plasma was performed in Cohort A (controls: 45, PD: 145), followed by analysis of seven polyamine metabolites in Cohort B (controls: 49, PD: 186, progressive supranuclear palsy: 19, Alzheimer’s disease: 23). Furthermore, 20 patients with PD who were successively examined within Cohort B were studied using diffusion tensor imaging. In Cohort A, N8-acetylspermidine and N-acetylputrescine levels were significantly and mildly elevated in PD, respectively. In Cohort B, spermine levels and spermine/spermidine ratio were significantly reduced in PD, concomitant with hyperacetylation. Furthermore, N1,N8-diacetylspermidine levels had the highest diagnostic value, and correlated with H&Y, UPDRS-III, and axonal degeneration. The spermine/spermidine ratio in controls declined with age, but was consistently suppressed in PD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、パーキンソン病患者における血清ポリアミン代謝産物の濃度変化は、新たなパーキンソン病診断バイオマーカーとしてだけでなく、疾患重症度を推定することを可能とするサロゲーティングバイオマーカーとしての有用性が確認された。現在臨床応用のため、測定条件などの詳細な検討を進めている。
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