2023 Fiscal Year Final Research Report
Elucidation of the Molecular Basis of Axonal Branching Abnormalities in Amyotrophic Lateral Sclerosis Models
| Project/Area Number |
21K07411
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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) |
2021-04-01 – 2024-03-31
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| Keywords | ALS |
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| Outline of Final Research Achievements |
In this study, we optimized a differentiation culture protocol for autonomic and sensory neurons and confirmed axon bundle formation within microfluidic devices. Utilizing microfluidic devices, we conducted Axon-seq comparative analysis by separating cell bodies and axons to identify 16 genes associated with minimal impairment in motor neurons in the pathogenesis of ALS. Additionally, as an in vivo experimental model, we established FUS mutation knock-in mice and established stable colonies through backcrossing. By analyzing the neuromuscular junctions using proteomics, we were able to identify novel disease-related proteins. By accumulating insights at both cellular and organismal levels, we aim to identify molecules that could serve as novel therapeutic targets for ALS.
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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 |
これまでのALS病態研究は神経細胞体に注目したものが多く、ニューロンの特徴的な構造である軸索病態に真正面から取り組んだ研究はほとんどなかった。本研究はiPS細胞活用における問題点である発生と老化病態の違いにも留意しつつ、マウスやヒト剖検脳も駆使し、形態と機能の相関を検討し、軸索における恒常性維持機構の各機序の相互作用についても解析を進める。ALSの病態を軸索という構造・機能から捉えなおすことで、新たな治療法開発へとつなげることが期待される。
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