• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular pathogenesis of cerebral small vessel disease.

Research Project

Project/Area Number 22390174
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNiigata University

Principal Investigator

ONODERA Osamu  新潟大学, 脳研究所, 教授 (20303167)

Co-Investigator(Kenkyū-buntansha) SATO Toshiya  新潟大学, 脳研究所, 助教 (90359703)
NOZAKI Hiroaki  新潟大学, 医学部, 助教 (20547567)
豊島 靖子  新潟大学, 脳研究所, 准教授 (20334675)
Project Period (FY) 2010-04-01 – 2013-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2012: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
KeywordsCARASIL / 血液脳関門 / 脳小血管 / HTRA1 / 平滑筋細胞 / 周皮細胞 / 血管性認知症 / TGF-β / 微小循環 / モデルマウス / 炎症 / サイトカイ
Research Abstract

Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). HTRA1 belongs to the HTRA protein family, whose members have dual activities as chaperones and serine proteases and also repress transforming growth factor-beta (TGF-beta) family signaling. We investigated the molecular pathogenesis of CARASIL in HTRA1 null mouse. By immunohistochemical analysis we have found the alteration in cerebral small vessels in the model. This model mouse could be useful for the investigation of the pathogenesis of cerebral small vessel disease.

Report

(4 results)
  • 2013 Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (40 results)

All 2013 2012 2011 2010

All Journal Article (17 results) (of which Peer Reviewed: 3 results) Presentation (19 results) (of which Invited: 3 results) Book (4 results)

  • [Journal Article] A novel mutation in the HTRA1 gene causes CARASIL without alopecia2011

    • Author(s)
      Nishimoto Y, Shibata M, Nihonmatsu M, Nozaki H, Shiga A, Shirata A, Yamane K, Kosakai A, Takahashi K, Nishizawa M, Onodera O, Suzuki N
    • Journal Title

      Neurology

      Volume: 76(15) Pages: 1353-5

    • Related Report
      2013 Final Research Report
  • [Journal Article] Neurological picture. Neuroaxonal integrity evaluated by MR spectroscopy in a case of CARASIL2011

    • Author(s)
      Nishimoto Y, Shibata M, Onodera O, Suzuki N
    • Journal Title

      J Neurol Neurosurg Psychiatry

      Volume: 82(8) Pages: 860-1

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β12011

    • Author(s)
      Shiga A, Nozaki H, Yokoseki A, Nihonmatsu M, Kawata H, Kato T, Koyama A, Arima. K, Ikeda M, Katada S, Toyoshima Y, Takahashi H, Tanaka A, Nakano I, Ikeuchi T, Nishizawa M, Onodera O
    • Journal Title

      Hum Mol Genet

      Volume: 20(9) Pages: 1800-10

    • Related Report
      2013 Final Research Report
  • [Journal Article] 認知症学下-その解明と治療の最新知見-臨床編血管性認知症とその類縁疾患CADASIL(皮質下梗塞および白質脳症を伴う常染色体優性脳動脈症)とCARASIL(皮質下梗塞と白質脳症を伴う脳常染色体劣性動脈症)2011

    • Author(s)
      加藤泰介,西澤正豊,小野寺理
    • Journal Title

      日本臨床増刊認知症学(下)

      Pages: 320-324

    • Related Report
      2013 Final Research Report
  • [Journal Article] 【認知症:診断と治療の進歩】トピックス新規の認知症関連遺伝子の発見TGF-βファミリーシグナルの異常と遺伝性脳小血管病CARASILの分子病態の解析から2011

    • Author(s)
      野崎洋明,西澤正豊,小野寺理
    • Journal Title

      日本内科学会雑誌

      Volume: 100巻8号 Pages: 2207-2213

    • Related Report
      2013 Final Research Report
  • [Journal Article] 脳小血管病とは何か2011

    • Author(s)
      小野寺理
    • Journal Title

      臨床神経学

      Volume: 51巻6号 Pages: 399-405

    • NAID

      10031164020

    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Journal Article] 【血管性認知症のニューホライズン】遺伝性脳小血管病の病態機序から脳小血管病を探る2011

    • Author(s)
      小野寺理
    • Journal Title

      Dementia Japan

      Volume: 25巻1号 Pages: 24-31

    • Related Report
      2013 Final Research Report
  • [Journal Article] 血管性認知症とその類縁疾患 CADASIL(皮質下梗塞および白質脳症を伴う常染色体優性脳動脈症)とCARASIL(皮質下梗塞と白質脳症を伴う脳常染色体劣性動脈症)2011

    • Author(s)
      加藤泰介
    • Journal Title

      日本臨床 )増刊10 認知症学(下)

      Volume: 10 Pages: 320-324

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 新規の認知症関連遺伝子の発見 TGF-βファミリーシグナルの異常と遺伝性脳小血管病 CARASILの分子病態の解析から2011

    • Author(s)
      野崎洋明
    • Journal Title

      日本内科学会雑誌

      Volume: 100 Pages: 2207-2213

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 【血管性認知症のニューホライズン】 遺伝性脳小血管病の病態機序から脳小血管病を探る2011

    • Author(s)
      小野寺理
    • Journal Title

      Dementia Japan

      Volume: 25 Pages: 24-31

    • Related Report
      2011 Annual Research Report
  • [Journal Article] A novel mutation in the HTRA1 gene causes CARASIL without alopecia.2011

    • Author(s)
      Nishimoto Y,
    • Journal Title

      Neurology.

      Volume: 76 Issue: 15 Pages: 1353-1355

    • DOI

      10.1212/wnl.0b013e318215281d

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurological picture. Neuroaxonal integrity evaluated by MR spectroscopy in a case of CARASIL.2011

    • Author(s)
      Nishimoto Y,
    • Journal Title

      J Neurol Neurosurg Psychiatry.

      Volume: 82 Issue: 8 Pages: 860-861

    • DOI

      10.1136/jnnp.2010.240051

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1.2011

    • Author(s)
      Shiga A
    • Journal Title

      Hum Mol Genet.

      Volume: 20 Issue: 9 Pages: 1800-1810

    • DOI

      10.1093/hmg/ddr063

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 臨床トピックス遺伝性脳小血管病2010

    • Author(s)
      今野卓哉,小野寺理
    • Journal Title

      医学のあゆみ

      Volume: 235巻6号 Pages: 745-748

    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Journal Article] CARASILの分子病態機序2010

    • Author(s)
      野崎洋明,志賀篤,西澤正豊,小野寺理
    • Journal Title

      神経内科

      Volume: 72巻4号 Pages: 408-412

    • NAID

      40017170126

    • Related Report
      2013 Final Research Report 2010 Annual Research Report
  • [Journal Article] CARASILの分子病態学BRAIN and NERVE2010

    • Author(s)
      志賀篤,野崎洋明,西澤正豊,小野寺理
    • Journal Title

      神経研究の進歩

      Volume: 62巻6号 Pages: 595-599

    • Related Report
      2013 Final Research Report
  • [Journal Article] CARASILの分子病態学2010

    • Author(s)
      志賀篤, 野崎洋明, 西澤正豊, 小野寺理
    • Journal Title

      BRAIN and NERVE:神経研究の進歩

      Volume: 62巻6号 Pages: 595-599

    • Related Report
      2010 Annual Research Report
  • [Presentation] MRI features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy2013

    • Author(s)
      野崎洋明
    • Organizer
      AAN 65^<th> Annual meeting
    • Place of Presentation
      San diego.USA
    • Related Report
      2013 Final Research Report
  • [Presentation] MRI Features of Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy2013

    • Author(s)
      Nozaki H
    • Organizer
      American Academy of Neurology 65th Annual Meeting,
    • Place of Presentation
      San Diego アメリカ合衆国
    • Related Report
      2012 Annual Research Report
  • [Presentation] CARASILの分子病態機序2012

    • Author(s)
      小野寺理
    • Organizer
      第31回日本認知症学会学術集会
    • Place of Presentation
      つくば
    • Year and Date
      2012-10-26
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] 脳小血管病とは何か2012

    • Author(s)
      小野寺理
    • Organizer
      第134回日本神経学会東海北陸地方会
    • Place of Presentation
      金沢
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] CARASILの病態機序への考察2012

    • Author(s)
      野崎洋明
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-25
    • Related Report
      2013 Final Research Report 2012 Annual Research Report
  • [Presentation] Molecular pathogenesis of cerebral small vessel disease-lesson from CARASIL2012

    • Author(s)
      小野寺理
    • Organizer
      Stroke 2012
    • Place of Presentation
      Tokyo
    • Year and Date
      2012-04-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 脳小血管病の分子病態機序を探る2012

    • Author(s)
      小野寺理
    • Organizer
      第10回首都圏脳卒中フォーラム
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Molecular pathogenesis of cerebral small vessel disease - lesson from CARASIL.2012

    • Author(s)
      小野寺理
    • Organizer
      Stroke 2012
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 片側アレルにのみHTRA1 ミスセンス変異を有する例でも脳小血管病を引き起こす2012

    • Author(s)
      野崎洋明
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] 遺伝性脳小血管病の分子病態 update2012

    • Author(s)
      野崎洋明
    • Organizer
      J-CAN2012
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] TGF-βファミリーシグナルの異常と脳小血管病2011

    • Author(s)
      小野寺理
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
    • Related Report
      2013 Final Research Report 2011 Annual Research Report
  • [Presentation] Novel molecular mechanism for hereditary cerebral small-vessel disease2010

    • Author(s)
      小野寺理
    • Organizer
      BMB2010
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Novel molecular mechanism for hereditary cerebral small-vessel disease2010

    • Author(s)
      小野寺理
    • Organizer
      BMB2010
    • Place of Presentation
      神戸(招待講演)
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] HTRA1 controls BMP2/4 signaling via cleavage of proBMP2/42010

    • Author(s)
      H NOZAKI, A. SHIGA, M. NIHONMATSU, A. KOYAMA, O ONODERA, M. NISHIZAWA
    • Organizer
      Implication for molecular pathogenesis of hereditary cerebral small vessel disease NEUROSCIENCE 2010
    • Place of Presentation
      San Diego.USA
    • Year and Date
      2010-11-14
    • Related Report
      2013 Final Research Report
  • [Presentation] HTRA1 controls BMP2/4 signaling via cleavage of proBMP2/4 : Implication for molecular pathogenesis of hereditary cerebral small vessel disease2010

    • Author(s)
      H.NOZAKI, A.SHIGA, M.NIHONMATSU, A.KOYAMA, O.ONODERA, M.NISHIZAWA
    • Organizer
      NEUROSCIENCE 2010
    • Place of Presentation
      San Diego
    • Year and Date
      2010-11-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] 遺伝性血管性認知症2010

    • Author(s)
      小野寺理
    • Organizer
      第29回日本認知症学会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-11-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 遺伝性血管性認知症2010

    • Author(s)
      小野寺理
    • Organizer
      第29回日本認知症学会
    • Place of Presentation
      名古屋(招待講演)
    • Year and Date
      2010-11-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] TGF-β経路は遺伝性脳小血管病で特異的に活性化される(TGF-βpathway is specifically activated in hereditary cerebral small-vessel disease)2010

    • Author(s)
      二本松萌,志賀篤,野崎洋明,西澤正豊,小野寺理
    • Organizer
      日本生化学会大会・日本分子生物学会年会合同大会83回・33回
    • Place of Presentation
      神戸
    • Related Report
      2013 Final Research Report
  • [Presentation] TGF-β経路は遺伝性脳小血管病で特異的に活性化される(TGF-β pathway is specifically activated in hereditary cerebral small-vessel disease)2010

    • Author(s)
      二本松萌, 志賀篤, 野崎洋明, 西澤正豊, 小野寺理
    • Organizer
      日本生化学会大会・日本分子生物学会年会合同大会83回・33回
    • Place of Presentation
      神戸
    • Related Report
      2010 Annual Research Report
  • [Book] Annual Review神経2011巻CARASILの臨床・病理像と病態機序2011

    • Author(s)
      野崎洋明,西澤正豊,小野寺理
    • Publisher
      中外医学社
    • Related Report
      2013 Final Research Report
  • [Book] Annual Review神経2011巻CARASILの臨床・病理像と病態機序2011

    • Author(s)
      野崎洋明
    • Total Pages
      9
    • Publisher
      中外医学社
    • Related Report
      2011 Annual Research Report
  • [Book] University of Washington, Seattle; CARASIL. GeneReviews2010

    • Author(s)
      Onodera O, Nozaki H, Fukutake T.In : Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP
    • Publisher
      Seattle (WA)(Internet)
    • Related Report
      2013 Final Research Report
  • [Book] CARASIL GeneReviews^<TM>2010

    • Author(s)
      Onodera O, Nozaki H, Fukutake T
    • Publisher
      In : Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, Seattle (WA) : University of Washington, Seattle(Internet)
    • Related Report
      2010 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi