| Project/Area Number |
17K16403
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Meijo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | クロザピン / プロテオーム / 薬理学 |
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| Outline of Final Research Achievements |
To identify the molecules involved in the pharmacological mechanism of clozapine (CLZ), an effective antipsychotic for treatment-resistant schizophrenia, comprehensive protein expression analysis was performed using brain tissue of disease model mice. Differentially expressed proteins involved in long-term potentiation and insulin signaling pathway in the prefrontal cortex (PFC), viral myocarditis and adrenergic signaling in cardiomyocytes in the nucleus accumbens (NAc), inositol phosphate metabolism in the striatum (STR), and ErbB and neurotrophin signaling pathway in the hippocampus (HIP) were identified as clozapine-reactive molecules. Phencyclidine (PCP), a non-competitive N-methyl-D-aspartate receptor antagonist and can reproduce a schizophrenia-like psychosis, and CLZ commonly affected molecules involved in the synaptic vesicle cycle in both PFC and HIP, neurological diseases (e.g. Alzheimer disease, Parkinson disease, Huntington diseases) in NAc, and the proteasome in STR.
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| Academic Significance and Societal Importance of the Research Achievements |
統合失調症の病態やクロザピンの治療効果と副作用に関連すると示唆されるタンパク質の発現変化および関連するパスウェイが同定された。これらの分子機能の修飾により表現型に与える影響を細胞・組織・臓器・個体レベルで詳細に検討することで、既存の副作用を克服した安全性の高い新たな治療法の開発に資する。効果的かつ安全な薬物治療の提供を実現することにより、患者・家族の精神的・経済的負担を軽減し、医学・社会への還元につながると考えられる。
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