2021 Fiscal Year Final Research Report
Elucidation of the mechanism of receptor tyrosine kinase ALK for neural axon regeneration
Project/Area Number |
19K18461
|
Research Category |
Grant-in-Aid for Early-Career Scientists
|
Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56020:Orthopedics-related
|
Research Institution | Nagoya University |
Principal Investigator |
Machino Masaaki 名古屋大学, 医学部附属病院, 病院助教 (70807510)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Keywords | 神経軸索 / 受容体型チロシンキナーゼ / ALK / 神経再生 |
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.
|
Free Research Field |
神経科学
|
Academic Significance and Societal Importance of the Research Achievements |
神経軸索再生の分子機構は十分に解明されていないのが現状である。神経系において特異的に発現の見られる受容体型チロシンキナーゼ(RTK)およびそれらのリガンドは、神経系の発生、分化、生存維持など多彩な生物学的機能を有している。未分化リンパ腫キナーゼ(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。本研究は神経軸索再生を主眼においているが、本研究のもたらす成果は、生理的可塑性の分子基盤の解明など、神経科学にブレイクスルーをもたらす可能性を秘めている。
|