Elucidation of neuroprotection and neural axon regeneration mechanism by PACAP

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09262
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: University of Tsukuba
• Principal Investigator: RAKWAL RANDEEP 筑波大学, 体育系, 教授 (70590850)
• Co-Investigator(Kenkyū-buntansha): 柴藤 淳子 湘南医療大学, 臨床医学研究所, 研究員 (10611121) ; 塩田 清二 湘南医療大学, 薬学部医療薬学科, 教授 (80102375)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: PACAP / CRMP2 / PAC1R

Outline of Final Research Achievements

Although dephosphorylation of CRMP2 by Pac1 receptor-mediated PI3K/AKT and MEK/ERK is important for PACAP-induced projection elongation, details of PACAP-induced projection elongation including CRMP2 dephosphorylation by GSK-3β, CDK5 and Rho/ROCK are unclear. Since CRMP2 dephosphorylation is detected within 3 hours of PACAP addition, we considered it important to identify initial factors involved in CRMP2 dephosphorylation effect by PACAP and performed high-throughput omics analyses. Many important regulators involved in neurite outgrowth, including known ones, were detected, and factors that may be involved in CRMP2 dephosphorylation were identified. Though this research could not confirm exact role and position of CRMP2 in PACAP mediated cell elongation, it appears that its phosphorylation and de-phosphorylation has a correlation with neurite protrusion elongation through interplay of CDK5, which needs further investigation.

Free Research Field

オミックス解析

Academic Significance and Societal Importance of the Research Achievements

これまでの研究により、CRMP2のリン酸化が軸索誘導や軸索再生に関与していることが明らかにされている。本報告では、PC12細胞をモデルとしたPACAPのCRMP2の脱リン酸化による突起伸長作用の分子機構について明らかにすることを目的としてオミックス解析を行い、突起伸長作用に関与する初期因子を同定することができた。CRMP2の脱リン酸化作用がアルツハイマー病や多発性硬化症など、神経変性疾患の治療標的として注目されている。PACAPによるCRMP2のリン酸化抑制を促進するメカニズムについて新たな知見を得ることで、新規治療法の開発などに貢献できると考えている。