2020 Fiscal Year Final Research Report
Elucidation of the pathogenic mechanism in neuropsychiatric disorders by nuclear-cytoplasmic transport factors
| Project/Area Number |
18K15044
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 核－細胞質間輸送因子 / エストロゲン受容体 |
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| Outline of Final Research Achievements |
In most of the neuropsychiatric disorders, their pathogenic mechanisms are still unclear. Our aim is to clarify the regulation of brain function by importin-α1 and the pathogenesis of psychiatric-like behavioral abnormalities caused by its decreased expression. In this study, we mainly focused on the subcellular distribution and shuttling of estrogen receptor-α (ERα). Our research has demonstrated that Transportin-2 controls ERα nucleocytoplasmic shuttling by cytoplasmic retention and inhibition of importin-α/β1-dependent nuclear import, and thus plays a critical role in the proper regulation of the biological functions of ERα.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
ERαは、主に核に存在する核内受容体であるが、核－細胞質間を常にシャトルしており、そのシャトルがエストロゲンシグナル伝達経路にとって非常に重要である。また、エストロゲンは、脳の海馬で高濃度に存在しており、スパインの密度と構造の変化を引き起こすことで認知機能を高める作用があることが報告されている。本研究により、ERαの核－細胞質間シャトリングメカニズムの解明や乳がん及び精神疾患の治療法の開発や創薬への応用が期待される。
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