| Project/Area Number |
17H06752
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Research Collaborator |
KADOMATSU kenji
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 受容体型チロシンキナーゼ / 未分化リンパ腫キナーゼ / 神経軸索 / 受容体型チロシンキナーゼ（RTK） / 未分化リンパ腫キナーゼ（ALK） / 神経軸索再生 / 受容体型チロシンキナー / RTK / ALK / axonal regeneration / axonal elongation / axonal sprouting |
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| Outline of Final Research Achievements |
Anaplastic lymphoma kinase (ALK) is a receptor type tyrosine kinase (RTK) that is expressed in neurons of the central and peripheral nervous systems. We investigated whether the ASP3026 as inhibitor of ALK and knocking down of ALK by siRNA suppress the outgrowth of adult mouse dorsal root ganglion (DRG) neurons, whether monoclonal antibody (mAb) 16-39 as an agonist of kinase activity of ALK promote axon outgrowth. In cultured DRG neuron, ALK was activated in elongating growth cones and sprouting axonal branches. Inhibition of ALK by ASP3026, reduced axonal elongation and branching in adult neurons. Inactivation of ALK by siRNA, reduced axonal elongation and branching in adult neurons. In contrast, mAb16-39 induced tyrosine phosphorylation of ALK, activation of ALK by mAb16-39, and promoted axonal elongation and sprouting. ALK significantly enhanced axonal elongation and branching. Taken together, our data indicate pivotal roles of RTK pathway in neural development or its repair.
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| Academic Significance and Societal Importance of the Research Achievements |
未分化リンパ腫キナーゼ（ALK）は受容体チロシンキナーゼ（RTK）の1つであり、特定の神経細胞集団に対して増殖、生存維持などの作用を持つ受容体として機能するとされるが、詳しい機能はいまだ不明である。本研究から得られて研究結果はALKの活性を調節している機構を解明し、ALKを標的とする神経再生治療法の開発に寄与する可能性を秘めている。
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