Molecular mechanism of neuropotection and axonal elongation by PACAP

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11597
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hoshi University
• Principal Investigator: Hirabayashi Takahiro 星薬科大学, 先端生命科学研究所, 寄附講座等講師 (40297015)
• Co-Investigator(Kenkyū-buntansha): 竹ノ谷 文子 星薬科大学, 薬学部, 准教授 (30234412)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: PACAP / PAC1-R / 虚血 / 神経細胞死 / 軸索伸長

Outline of Final Research Achievements

The pituitary adenylate cyclase-activating polypeptide PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide) is known to have axon elongation effects on neurons after injury. In the present study, we analyzed the molecular mechanism of PACAP-induced axon elongation in PC12 cells, which are frequently used as a model for axon elongation. It is revealed that PACAP-induced axon elongation was mediated by the activation of Akt by PI3K and the inactivation of GSK-3β by the activation of Akt and the subsequent decrease in the inactive form of phosphorylated CRMP2.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではPACAPによる軸索伸長作用の分子機構の一端を明らかにすることが出来た。さらなる解析が必要であるが、今後詳細な解析を進めることにより、神経損傷後の軸索伸長、神経細胞死抑制における新たな標的分子の発見ができると思われる。その結果、PACAPの虚血に対する救急医療領域での臨床応用への道が開かれるとともに、新規医薬品の開発につながることが期待できる。