The role of molecular chaperone VCP in excitotoxin-induced cell death.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: Furukawa Ayako 鈴鹿医療科学大学, 薬学部, 助教 (10455537)
• Co-Investigator(Kenkyū-buntansha): 郡山 恵樹 鈴鹿医療科学大学, 薬学部, 准教授 (70397199)
• Research Collaborator: CHIBA yoichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 興奮毒性 / VCP / 酸化ストレス / 細胞死

Outline of Final Research Achievements

In the present study, we focused on the role of valosin containing protein(VCP) in excitotoxin-induced cell death. We elucidated that VCP was increased in reactive astrocyte in excitotoxin-treated rat hippocampus. In primary mixed glial cultures, Eeyarestatin I, which is an inhibitor of VCP, was shown to promote cell death by glutamate. These results suggest that VCP may act as a cytoprotective factor in glial cells. Eeyarestatin I induced ER stress marker proteins in glial cells, no induction of them were observed in eeyarestatin and glutamate-treated cells. Thus, the cytoprotective effect of VCP may not be an ER stress response.

Free Research Field

生化学、神経科学

Academic Significance and Societal Importance of the Research Achievements

興奮毒性は、神経細胞の過剰な興奮性シグナル伝達によって生じる。低酸素性虚血性脳症は、周産期の一過性の低酸素と虚血による興奮毒性をきっかけに、てんかんなどの後遺症を引き起こす。興奮毒性により、どのような分子が関与して脳内の環境が変化するのか、それらの分子が治療標的となり得るかを明らかにすることは、周産期の傷害をきっかけに生じる神経学的後遺症を改善する上で重要であると考える。