Study to develop therapeutic strategy of neurodegenerative disorders by targeting on CRMP
| Project/Area Number |
18K06511
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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 46020:Anatomy and histopathology of nervous system-related
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| Research Institution | Waseda University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 神経変性疾患 / 神経再生 / マウスモデル / パーキンソン病 / リン酸化 / モデルマウス / 脊髄損傷 / 神経損傷 |
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| Outline of Final Research Achievements |
We conducted experimental research to develop therapeutic strategy for the treatment of patients with neurodegenerative disorders by targeting on CRMPs which are involved in neural development and regeneration. Using mice, we examined the effect of loss of CRMP4 and suppression of CRMP2 phosphorylation on neural degeneration and regeneration. We found that loss of CRMP4 suppressed the decline of dopaminergic neurons in substantia nigra after 6-OHDA injection into striatum. By inhibiting CRMP2 phosphorylation, regeneration of optic nerve was promoted after optic nerve injury. Suppressed degeneration of axonal terminals of dopaminergic neurons in substantia nigra was also observed after MPTP treatment, suggesting a potential of therapeutic strategy to treat neurodegenerative disorders by manipulation of CRMPs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、神経発生や神経再生に関与しているCRMPをターゲットとした神経変性疾患の治療を目指して行なわれた。結果として、6-OHDAを線条体に注入するパーキンソン病(PD)モデルにおいて、CRMP4遺伝子欠損がドーパミン神経(DN)脱落を抑制することが示された。また、CRMP2のリン酸化抑制により、視神経損傷後の視神経変性が抑制され、神経再生が促進することが明らかとなった。さらに、CRMP2のリン酸化抑制がMPTP薬剤誘導型PDモデルでもDNの脱落を抑制し、神経軸索の変性を抑止した。以上実験結果から、神経変性疾患の治療法としてCRMPをターゲトとした創薬が有用である可能性が示された。
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Report
(4 results)
Research Products
(5 results)
