Development of a new therapy for brain edema: study for regulation of AQP4 as a molecular target

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04688
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Keio University
• Principal Investigator: YASUI MASATO 慶應義塾大学, 医学部(信濃町), 教授 (90246637)
• Co-Investigator(Renkei-kenkyūsha): HIRANO Yoshinori 国立研究開発法人理化学研究所, 生命システム研究センター, 研究員 (50360631)
• Research Collaborator: ABE Yoichiro 慶應義塾大学, 医学部(信濃町), 専任講師 (10317331)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アクアポリン / 脳浮腫 / グリア

Outline of Final Research Achievements

Aquaporin4 (AQP4) has been shown to be involved in the development of brain edema. We recently developed a high throughput-screening system for AQP4, as a target molecule for the treatment of brain edema. In this project, we identified at least one chemical compound that inhibits AQP4, by using a stopped flow apparatus with AQP4 proteoliposome. Computer based docking study revealed that this chemical may interact with the extracelluar domain of AQP4. Next, we examined molecular mechanisms of AQP4 endocytosis to understand the molecular regulation of AQP4. We have identified three signals for; i) trafficking to the plasma membranes, ii) protein stability and iii) sorting to lysosomes.

Free Research Field

医歯薬学