2020 Fiscal Year Final Research Report
Analysis of axonal pathomechanism in amyotrophic lateral sclerosis using human iPS cell-derived nerve organoid.
| Project/Area Number |
18K07519
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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 52020:Neurology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
Suzuki Naoki 東北大学, 大学病院, 助教 (70451599)
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| Co-Investigator(Kenkyū-buntansha) |
割田 仁 東北大学, 大学病院, 助教 (30400245)
青木 正志 東北大学, 医学系研究科, 教授 (70302148)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 筋萎縮性側索硬化症 / iPS細胞 / 軸索 |
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| Outline of Final Research Achievements |
RNA sequencing analysis of axonal fraction of nerve organoid revealed a gene, Fos-B, associated with the pathogenesis of FUS mutations. We demonstrated that Fos-B is involved in the formation of abnormal axon branching associated with FUS mutations in motor neurons using overexpression and inhibition experiments. Furthermore, using zebrafish overexpression of Fos-B and human autopsy spinal cord, we clarified the relationship between Fos-B and ALS pathology. These results were reported in EBioMedicine in 2019. We wrote a review on omics analysis of axons, which was published in Frontiers in Neuroscience in 2020. In 2021, we found decreased expression of Phox2B using TARDBP mutant iPS cells, the causative gene of ALS, and it was accepted by Stem Cell Reports. We will continue to investigate the axonal pathology underlying motor neuron vulnerability.
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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 |
ALS患者は日本で約1万人、世界で約35万人と想定され、高齢化に伴い増加傾向にある。人工呼吸器を使用しなければ2-5年で呼吸不全により死亡する予後不良の難病である。根本的な治療法が確立されていない。本研究はALSの初期から病変がみとめられる軸索の病態にフォーカスすることで早期治療介入が可能となると考えた。ALS軸索病態の鍵分子を明らかにすることで、新規治療法開発への道筋がつけられたと考えている。
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