| Project/Area Number |
16K08383
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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 | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
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| Research Collaborator |
ITOKAWA MASANARI
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 統合失調症 / カルボニルストレス / メチルグリオキサール / バイオマーカー / 治療抵抗性 / 治療抵抗性統合失調症 / carbonyl stress / カルボニル化タンパク質 / glycation / schizophrenia / methylglyoxal / argpyrimidine / Nrf2 pathway / glutathione / polysulfide / persulfide / carnosic acid / 診断マーカー / 翻訳後修飾 |
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| Outline of Final Research Achievements |
1.We determined the formation of protein carbonyl in the plasma of schizophrenic patients. Protein carbonyl levels in the plasma from schizophrenic patients were significantly higher than that from healthy subjects. Western blots analysis clearly showed that albumin and IgG were markedly carbonylated in the plasma of patients.2.We established practical method based on HPLC with fluorescence detection to measure low methylglyoxal(MGO) levels. MGO concentrations were measured in human plasma using the original method in order to demonstrate its utility.3.We observed marked accumulation of an approximately 56 kD protein, reactive to anti-argpyrimidine antibodies, in the red blood cells of some patients with refractory schizophrenia. This ARP-modified protein was purified from the blood of schizophrenic patients and identified as selenium binding protein 1 (SBP1) by LC-MS/MS.4.In the preliminary study, we found the accumulation of MGO levels and MGO-induced AGEs in the model mouse brain.
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| Academic Significance and Societal Importance of the Research Achievements |
治療抵抗性統合失調症患者の血液を用いて、バイオマーカーの探索を行った。本研究から得られた知見として、患者血漿中においてカルボニルタンパク質の有意な上昇と、患者赤血球中に、メチルグリオキサール(MGO)を前駆体として生成するアルグピリミジン構造を有する糖化タンパク質の蓄積を見出した。従って、カルボニルストレス性統合失調症と考えられる患者の割合は予想以上に多いことが示唆された。MGOが本疾患の原因物質である可能性が推定されたことから、今後、脳内タンパク質が糖化を受けることで生じるタンパク質機能や神経細胞構造の変化を詳細化することにより、本統合失調症の発症機序解明の糸口が見つかることが期待される。
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