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Pathomechanism of cerebral small vessel disease due to disturbance of transendocytosis

Research Project

Project/Area Number 26461276
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKyoto 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
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsCADASIL / 遺伝性脳小血管病 / NOTCH3 / transendocytosis / Notch / 脳小血管病 / Notch3 / trasnendocytosis
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.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (28 results)

All 2017 2016 2015 2014 Other

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (17 results) (of which Int'l Joint Research: 7 results,  Invited: 5 results) Remarks (1 results)

  • [Journal Article] New diagnostic criteria for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukocencephalopathy in Japan.2017

    • Author(s)
      Mizuta I, Hosomi-Watanabe A, Koizumi T, Mukai M, Hamano A, Tomii Y, Kondo M, Nakagawa M, Tomimoto H, Hirano T, Uchino M, Onodera O, Mizuno T
    • Journal Title

      J Neurol Sci

      Volume: 381 Pages: 62-67

    • DOI

      10.1016/j.jns.2017.08.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CADASILの臨床像と遺伝子異常2017

    • Author(s)
      渡邉 明子, 水田 依久子, 水野 敏樹
    • Journal Title

      神経内科

      Volume: 87 Pages: 630-637

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy with a Novel NOTCH3 Cys323Trp Mutation Presenting Border-Zone Infarcts: A Case Report and Literature Review2016

    • Author(s)
      Maya Tojima, Satoshi Saito, Yumi Yamamoto, Toshiki Mizuno, Masafumi Ihara, and Hidetoshi Fukuda.
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 25 Issue: 8 Pages: 128-130

    • DOI

      10.1016/j.jstrokecerebrovasdis.2016.05.013

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Japanese CADASIL kindred with a novel two-base NOTCH3 mutation.2016

    • Author(s)
      Suda, Satoshi; Okubo, Seiji; Ueda, Masayuki; Sowa, Kota; Abe, Arata; Aoki, Junya; Muraga, Kanako; Suzuki, Kentaro; Sakamoto, Yuki; Mizuta, Ikuko; Mizuno, Toshiki; Kimura, Kazumi.
    • Journal Title

      Eur J Neurol

      Volume: 23 Issue: 5 Pages: 32-34

    • DOI

      10.1111/ene.12977

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] CADASIL Presenting as Acute Bilateral Multiple Subcortical Infarcts without a Characteristic Temporal Pole or Any External Capsule Lesions2016

    • Author(s)
      Takashi Ando, Yoji Goto, Kazuo Mano, Akihiko Ueda, Yukio Ando, Ikuko Mizuta and Toshiki Mizuno
    • Journal Title

      Internal Medicine

      Volume: 55 Issue: 19 Pages: 2873-2876

    • DOI

      10.2169/internalmedicine.55.7123

    • NAID

      130005605891

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct molecular mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL.2016

    • Author(s)
      Nozaki H, Kato T, Nihonmatsu M, Saito Y, Mizuta I, Noda T, Koike R, Miyazaki K, Kaito M, Ito S, Makino M, Koyama A, Shiga A, Uemura M, Sekine Y, Murakami A, Moritani S, Hara K, Yokoseki A, Kuwano R, Endo N, Momotsu T, Yoshida M, Nishizawa M, Mizuno T, Onodera O
    • Journal Title

      Neurology

      Volume: 86 Issue: 21 Pages: 1-10

    • DOI

      10.1212/wnl.0000000000002694

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Very prolonged capsular warning syndrome.2015

    • Author(s)
      Makita N, Yamamoto Y, Nagakane Y, Ashida S, Mizuno T.
    • Journal Title

      J Neurol Sci. 2015

      Volume: 352 Issue: 1-2 Pages: 115-116

    • DOI

      10.1016/j.jns.2015.03.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 皮質下性認知症の現代的捉え方 遺伝性脳小血管病からの解析2015

    • Author(s)
      水野敏樹
    • Journal Title

      BRAIN and NERVE

      Volume: 67 Pages: 403-412

    • Related Report
      2015 Research-status Report 2014 Research-status Report
  • [Journal Article] 脳卒中臨床の最新の話題 遺伝性脳小血管病(CADASIL,CALASIL)2015

    • Author(s)
      向井麻央,水野敏樹
    • Journal Title

      医学のあゆみ

      Volume: 254 Pages: 113-117

    • Related Report
      2015 Research-status Report
  • [Journal Article] 脳卒中と遺伝子Update CADASIL2014

    • Author(s)
      渡邉 明子、水野敏樹
    • Journal Title

      分子脳血管病

      Volume: 13 Pages: 175-178

    • Related Report
      2014 Research-status Report
  • [Presentation] Lesson from the hereditary cerebral small vessel disease2017

    • Author(s)
      Toshiki Mizuno
    • Organizer
      international conference of Neurology and brain disorders conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] NEW DIAGNOSTIC CRITERIA FOR CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOCENCEPHALOPATHY IN JAPAN2017

    • Author(s)
      T. MizunoI. Mizuta  A. Watanabe-Hosomi  T. Koizumi  M. Mukai  A. Hamano Y. Tomii  M. Kondo  M. Nakagawa  T. Hirano  M. Uchino  O. Onodera H. Tomimoto
    • Organizer
      World Congress of Neurology 2107
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] CADASILの発症機序と今後の展開2017

    • Author(s)
      水野敏樹
    • Organizer
      第49回日本動脈硬化学会総会・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Endothelin1による白質脳症の機序2017

    • Author(s)
      水野敏樹水田依久子、渡邊明子、向井麻央、小泉崇
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A case report of heterozygous Pro285Leu HTRA1 mutation2016

    • Author(s)
      T Mizuno , I Mizuta, M Makino, H Nozaki, T Kato, O Onodera
    • Organizer
      The 8th Vas-Cog World Conference
    • Place of Presentation
      Amsterdam, Netherland
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] CADASILはどこまで解明されたか2016

    • Author(s)
      水野敏樹
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 遺伝性の血管性認知症 ーCADASILとCARASILー2016

    • Author(s)
      水野敏樹
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] CADASILにおける脳血管反応異常とそれに基づく治療戦略2016

    • Author(s)
      水野敏樹
    • Organizer
      第41回日本脳卒中学会総会
    • Place of Presentation
      札幌
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 日本人に即したCADASILスケール作成およびその有効性の検討.2016

    • Author(s)
      小泉崇 向井麻央,濱野愛,渡邊明子,水田依久子,水野敏樹.
    • Organizer
      第7回日本脳血管・認知症学会学術大会
    • Place of Presentation
      金沢
    • Related Report
      2016 Research-status Report
  • [Presentation] 認知症を伴うCADASIL症例のスクリーニング認知機能検査にみられる特徴2015

    • Author(s)
      手塚 陽子, 近藤 正樹,水野 敏樹
    • Organizer
      第6回日本脳血管・認知症学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2015-09-19
    • Related Report
      2015 Research-status Report
  • [Presentation] Consideration of Issues Related to Pre-and Post-Genetic Test for CADASIL2015

    • Author(s)
      Ikuko Mizuta, Mao Mukai, Akiko Watanabe, Ai Hamano, Tomoyuki Ohara, Tomokatsu Yoshida, Toshiki Mizuno
    • Organizer
      The 7th Vas-Cog World Conference
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-09-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Validation of Japanese Diagnostic Criteria for Cerebral Autosomal Dominant Arteriopathy with Subcorical Infarcts and Leukocencephalopathy2015

    • Author(s)
      Toshiki Mizuno, Ikuko Mizuta, Akiko Watanabe, Ai Hamano, Mao Mukai, Masaki Kondo, Masanori Nakagawa, Hidekazu Tomimoto, Makoto Uchino, Osamu Onodera.
    • Organizer
      The 7th Vas-Cog World Conference
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-09-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A Case Report of CADASIL with a Homozygous NOTCH3 Mutation Arg544Cys2015

    • Author(s)
      Mao Mukai, Daisuke N,Yukie Kushimura,Yu-ichi Noto, Tomoyuki Ohara, Ikuko Mizuta, Toshiki Mizuno.
    • Organizer
      The 7th Vas-Cog World Conference
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-09-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 塩酸ロメリジンによるCADASIL患者における脳梗塞発症に対する予防効果2014

    • Author(s)
      水野敏樹,濱野 愛,渡邉明子,水田依久子,近藤正樹,中川正法
    • Organizer
      第32回日本神経治療学会総会.2014年11月20-22日;東京
    • Place of Presentation
      東京
    • Year and Date
      2014-11-20 – 2014-11-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 水痘再感染による水痘帯状疱疹ウイルス髄膜炎の一例2014

    • Author(s)
      小島雄太,徳田直輝,中川有夏,中井章淳,能登祐一,村西 学,笠井高士,中川正法,水野敏樹
    • Organizer
      第19回日本神経感染症学会総会
    • Place of Presentation
      金沢
    • Year and Date
      2014-09-04 – 2014-09-06
    • Related Report
      2014 Research-status Report
  • [Presentation] CADASILのNOTCH3遺伝子変異分布と臨床像との関連性について2014

    • Author(s)
      水田依久子,渡邉明子,濱野愛,中川正法,水野敏樹.
    • Organizer
      第5回日本血管性認知障害研究会
    • Place of Presentation
      京都
    • Year and Date
      2014-08-23
    • Related Report
      2014 Research-status Report
  • [Presentation] CADASIL 患者における活性化血小板マーカー(PAC-1, CD62p)の検討2014

    • Author(s)
      藤並 潤、大原 亮、森井 芙貴子、水野 敏樹
    • Organizer
      第5回日本血管性認知障害研究会
    • Place of Presentation
      京都
    • Year and Date
      2014-08-23
    • Related Report
      2014 Research-status Report
  • [Remarks] 京都府立医科大学神経内科

    • URL

      http://www.neurology-kpum.com/

    • Related Report
      2017 Annual Research Report 2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2022-01-27  

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