2023 Fiscal Year Final Research Report
The development of the treatment of neurodegenerative disorders based on the functional analysis of CRMP2
| Project/Area Number |
18K15457
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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 52020:Neurology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2021-11-01 – 2024-03-31
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| Keywords | CRMP / 神経変性疾患 |
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| Outline of Final Research Achievements |
Immunostaining of MSA showed that phosphorylated CRMP1/2 colocalized with α synuclein and LC3 in GCI. Total lysate in frozen MSA brains showed a decrease in phosphorylated CRMP1/2 in MSA compared to disease control but not in insoluble fraction. In CRMP2-deficient mice, a decrease in LC3II/I and an increase in lysosomal transport were observed, suggesting that CRMP2 modifies autophagy and lysosomal transport and accumulates in GCI. On the other hand, increased CRMP1 phosphorylation was observed in ALS, and the inhibition of CRMP1 phosphorylation prolonged survival and improved motor function in ALS model mouse. Based on these findings, it is thought that inhibition of phosphorylation of CRMP1 is a therapeutic target for ALS.
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| Free Research Field |
神経内科
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では，軸索ガイダンスプロテインであるセマフォリン3Aの下流分子であるCRMPのリン酸化変化が多系統萎縮症、筋萎縮性側索硬化症で認められることを発見し，さらにその知見に基づき，CRMP非リン酸化マウスを作製し，筋萎縮性側索硬化症モデルマウスと掛け合わせることにより，CRMPの非リン酸化が筋萎縮性側索硬化症の表現型を改善することを示した．これらの研究をは，神経変性疾患におけるCRMPをターゲットとした治療法開発の礎になると考えられる．
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