2023 Fiscal Year Final Research Report
A compound screening targeting CIDE-A - AMPK pathway in the endoplasmic reticulum stress-related diseases
| Project/Area Number |
21K06864
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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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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 小胞体ストレス / 甲状腺濾胞細胞 / 細胞生存 / CIDE-A / イメグリミン |
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| Outline of Final Research Achievements |
In this study,we revealed that 1)a newly discovered unfolded protein response gene "cell death-Inducing DNA fragmentation factor-like Effector-A (CIDE-A)", which is associated with the adaptation to the chronic endoplasmic reticulum (ER) stress, is regulated positively by forkhead box protein O1(Foxo1) and 2) the cell death induced by the over-expression of CIDE-A is amplified by suppression of CIDE-C,, another CIDE family protein. We also elucidated that imeglimin, a brand new orally drug for type 2 diabetes mellitus,which is thought to improve mitochondrial function reduced ER stress associated death of rat thyroid follicular cell line PCCL3 alog with increased BiP expression and decreased CIDE-A elevation.
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| Free Research Field |
医学
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| Academic Significance and Societal Importance of the Research Achievements |
インスリン遺伝子異常による糖尿病や家族性中枢性尿崩症、遺伝性甲状腺機能低下症等の内分泌疾患や遺伝性神経変性疾患等を含む小胞体ストレス関連疾患は不可逆的であり、病態完成を抑制する治療法確立が求められている。今回の我々の研究成果は、これらの疾患の根本原因である細胞死に関与する新規小胞体ストレス応答因子であるCIDE-Aの制御機構解明に寄与するものである。また、今回明らかにしたイメグリミンによる甲状腺濾胞細胞の小胞体ストレス関連死抑制は、膵β細胞においても同様の報告がされており、広く内分泌細胞保護に応用できる可能性があることから、小胞体ストレス関連疾患の治療法開発に貢献するものと期待される。
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