Pathomechanism of cerebral small vessel disease due to disturbance of transendocytosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Mizuno Toshiki 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30264782)
• Co-Investigator(Kenkyū-buntansha): 田中 雅樹 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80264753) ; 水田 依久子 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80397760) ; 大原 亮 京都府立医科大学, 医学(系)研究科(研究院), 助教 (80636986)
• Research Collaborator: Mukai Mao 京都府立医科大学, 医学研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: CADASIL / 遺伝性脳小血管病 / NOTCH3 / transendocytosis

Outline of Final Research Achievements

The aim of this study is to clarify the pathomechanism of Cerebral Autosomal Dominant Arteriopathy with Sub- cortical Infarcts and Leukoencephalopathy (CADASIL). We hypothized that endocytosis into ligand expressing cell might be disturbed after activation of notch signaling in CADASIL We analyzed the endocytosis of fragment of NOTCH3 extracellular domain into transient Jagged1 expressing cell. The fragment of wild NOTCH3 extracellular domain was found in the Jagged1 expressing cell. In contrast, the fragment of mutant NOTCH3 extracellular domain was not found in the Jagged1 expressing cell. These results supported that endocytosis into ligand expressing cell is disturbed in CADASIL.

Free Research Field

神経内科学