Molecular pathology of moyamoyta disease and its translational research toward prevention and drug development

2015 Fiscal Year Final Research Report

• Project/Area Number: 25253047
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Epidemiology and preventive medicine
• Research Institution: Kyoto University
• Principal Investigator: KOIZUMI Akio 京都大学, 医学(系)研究科(研究院), 教授 (50124574)
• Co-Investigator(Kenkyū-buntansha): SONE Masakatsu 京都大学, 大学院医学研究科, 特定准教授 (40437207) ; MIYAMOTO Susumu 京都大学, 大学院医学研究科, 教授 (70239440) ; TAKAGI Yasushi 京都大学, 大学院医学研究科, 准教授 (40312227) ; HABU Toshiyuki 武庫川女子大学, 生活環境学部, 准教授 (70346071) ; YAMAZAKI Satoru 独立行政法人国立循環器病研究センター, 細胞生物学部, 室長 (70348796) ; HARADA Koji 京都大学, 大学院医学研究科, 准教授 (80452340) ; HITOMI Toshiaki 聖マリアンナ医科大学, 医学部, 准教授 (90405275)
• Project Period (FY): 2013-10-21 – 2016-03-31
• Keywords: 分子遺伝疫学 / 予防医学 / 社会医学 / 衛生学 / 医歯薬学

Outline of Final Research Achievements

We found that RNF213 is the susceptibility gene for moyamoya disease (MMD and its R4810K variant is the founder mutation among Asians. In the present project、we expanded the research in three fields. First, we investigated association of R4810K with coronary artery disease (CAD), which is often complicated with MMD and found strong association between RNF213 R4810K and CAD. In the transgenic animal study, overexpression of R4757K in endothelial cells (human R4810K orthologue) was found to inhibit angiogenesis in brain under the hypoxia. Finally, we found that a small molecule which inhibits ATPase activity by interacting with A module is a promising candidate for drug development.

Free Research Field

環境衛生学