Application of axon and synaptic modifier GPR3 for the treatment of neuronal circuit reconstruction after central nervous system injury.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Hiroshima University
• Principal Investigator: Tanaka Shigeru 広島大学, 医系科学研究科(医), 准教授 (20512651)
• Co-Investigator(Kenkyū-buntansha): 細見 直永 広島大学, 原爆放射線医科学研究所, 研究員 (70363190)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: GPR3 / 緑内障 / 神経再生 / cAMP

Outline of Final Research Achievements

GPR3 is a G protein-coupled receptor that is abundantly expressed in neurons and has　potential to activate Gαs protein in the absence of ligand. The principal investigator has previously analyzed and reported the function of GPR3 in neurons. In this study, using primary cultured neurons, we newly found that GPR3 promotes PI3K-dependent neurite outgrowth and neuronal polarity formation. Furthermore, we confirmed GPR3 expression in mouse retinal neurons and demonstrated its relevance to stress tolerance to aging and ischemia, and that GPR3 gene transfer to retinal ganglion cells promotes axonal regeneration after optic nerve axonal injury.

Free Research Field

神経科学、神経薬理学、再生医療

Academic Significance and Societal Importance of the Research Achievements

本研究では神経細胞におけるGPR3の新たな機能やメカニズムについて解明した。さらに、GPR3の網膜神経細胞生存・軸索再生への寄与が明らかになった。GPR3の多様な機能については、さらなるメカニズムの解析が必要であるが、緑内障をはじめとする軸索変性疾患の病態メカニズム解明や、軸索再生療法などへの応用への基盤となるかもしれない。