2020 Fiscal Year Final Research Report
Research on PD pathogenesis based on polyamine metabolism using multiomics analysis
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 |
Section | 特設分野 |
Research Field |
Complex Systems Disease Theory
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Research Institution | Juntendo University |
Principal Investigator |
Saiki Shinji 順天堂大学, 医学部, 准教授 (00339996)
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Project Period (FY) |
2018-07-18 – 2021-03-31
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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 |
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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Free Research Field |
神経内科学
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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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