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Strategies for overcoming vascular dementia focusing on dynamic functions of cerebral small vessels.

Research Project

Project/Area Number 16H02656
Research Category

Grant-in-Aid for Scientific Research (A)

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) 豊島 靖子  新潟大学, 脳研究所, 准教授 (20334675)
加藤 泰介  新潟大学, 脳研究所, 特任准教授 (30598496)
小山 哲秀  新潟大学, 医歯学系, 助教 (90622209)
野崎 洋明  新潟大学, 医歯学系, 助教 (20547567)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥46,670,000 (Direct Cost: ¥35,900,000、Indirect Cost: ¥10,770,000)
Fiscal Year 2018: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2017: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2016: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Keywords認知症 / 脳血管障害 / 脳小血管病 / 脳神経疾患 / 循環器 / 病理学 / 痴呆 / タンパク質 / CARASIL / HTRA1 / 蛋白質
Outline of Final Research Achievements

Overcoming dementia is an urgent task, and vascular dementia is one of the leading causes. Recently, a cerebral small vessel is noted and is called cerebral small vessel disease. Disorders of neural activity-dependent blood supply regulatory mechanisms have been advocated as the pathological condition. However, its molecular mechanism has not been well characterized. We isolated the causative gene for hereditary cerebral small vessel disease, HTRA1, and clarified that this disease is due to an increase in tissue growth factor signal. Furthermore, we defined the molecular pathogenesis of cerebral small vessel disease in mice with degeneration of smooth muscle and pericytes similar to sporadic cerebrovascular disease.

Academic Significance and Societal Importance of the Research Achievements

認知症の主因である脳血管性認知症の治療方法を見出すために,その機序を明らかとした点は大きい.また脳小血管病に関する研究領域を開拓し,今後の認知症治療研究への新たな方法を見出した.さらに小血管を保護するシーズを見出した.この成果により,現在,ヒトでの臨床応用を見据え,シーズの最適化を行うに至っている.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (32 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (24 results) (of which Int'l Joint Research: 8 results,  Invited: 6 results)

  • [Int'l Joint Research] National Institute of Mental Health(India)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Pennsylvania State University(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Histopathologic features of an autopsied patient with cerebral small vessel disease and a heterozygous HTRA1 mutation2018

    • Author(s)
      Ito Junko、Nozaki Hiroaki、Toyoshima Yasuko、Abe Takashi、Sato Aki、Hashidate Hideki、Igarashi Shuichi、Onodera Osamu、Takahashi Hitoshi、Kakita Akiyoshi
    • Journal Title

      Neuropathology

      Volume: 38 Issue: 4 Pages: 428-432

    • DOI

      10.1111/neup.12473

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL)2017

    • Author(s)
      Uemura M, Nozaki H, Onodera O.
    • Journal Title

      BRAIN and NERVE

      Volume: 69 Issue: 1 Pages: 25-33

    • DOI

      10.11477/mf.1416200631

    • ISSN
      1344-8129, 1881-6096
    • Year and Date
      2017-01-01
    • Related Report
      2016 Annual Research Report
  • [Journal Article] CARASIL families from India with 3 novel null mutations in theHTRA1gene2017

    • Author(s)
      Preethish-Kumar Veeramani、Nozaki Hiroaki、Tiwari Sarbesh、Vengalil Seena、Bhat Maya、Prasad Chandrajit、Onodera Osamu、Uemura Masahiro、Doniparthi Seshagiri、Saini Jitender、Nashi Saraswati、Polavarapu Kiran、Nalini Atchayaram
    • Journal Title

      Neurology

      Volume: 89 Issue: 23 Pages: 2392-2394

    • DOI

      10.1212/wnl.0000000000004710

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 特集 近年注目されている白質脳症 CARASIL-(Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)2017

    • Author(s)
      上村 昌寛、野崎 洋明、小野寺 理
    • Journal Title

      BRAIN and NERVE

      Volume: 69 Pages: 25-33

    • Related Report
      2017 Annual Research Report
  • [Journal Article] A CARASIL Patient from Americas with Novel Mutation and Atypical Features: Case Presentation and Literature Review2017

    • Author(s)
      Ibrahimi Muhammad、Nozaki Hiroaki、Lee Angelica、Onodera Osamu、Reichwein Raymond、Wicklund Matthew、El-Ghanem Mohammad
    • Journal Title

      Cerebrovascular Diseases

      Volume: 44 Issue: 3-4 Pages: 135-140

    • DOI

      10.1159/000477358

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] HTRA1活性低下による脳小血管病2019

    • Author(s)
      小野寺理
    • Organizer
      Stroke 2019
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 成人発症脳症血管病を呈する一卵性双生児に認めたCOL4A1スプライスサイト多型の検討2019

    • Author(s)
      酒井直子
    • Organizer
      第59回 日本神経学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The frequency of mutations in NOTCH3 or HTRA1 gene among 160 Japanese CSVD patients2019

    • Author(s)
      野崎洋明
    • Organizer
      第59回 日本神経学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 片頭痛を認める遺伝性脳小血管病の臨床的検討2019

    • Author(s)
      酒井直子
    • Organizer
      第46回頭痛学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 遺伝性脳小血管病における微小出血の特徴2018

    • Author(s)
      上村昌寛, 野崎洋明, 酒井直子先生, 小野寺理
    • Organizer
      第43回日本脳卒中学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] How are neurovascular units maintained in aging? From a study of HSCVD2017

    • Author(s)
      小野寺理
    • Organizer
      Brain Protein Aging and Dementia Control, 2nd International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳小血管病の分子病態:CARASILからのアプローチ2017

    • Author(s)
      小野寺理
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] タンパク質老化に寄与する脳小血管ユニットの異常 -非神経細胞の視点から-2017

    • Author(s)
      小野寺理
    • Organizer
      新学術領域研究[グリアアセンブリ][脳タンパク質老化]公開シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] CARASIL:HTRA1活性の低下と脳小血管病2017

    • Author(s)
      小野寺理
    • Organizer
      第49回日本動脈硬化学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 脳小血管の機能と疾病の分子病態2017

    • Author(s)
      小野寺理
    • Organizer
      第8回日本脳血管・認知症学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Molecular analysis of mutant high-temperature requirement serine protease A1 identified in patients with familial cerebral small vessel disease2017

    • Author(s)
      Uemura M, Nozaki H, Kato T, Koyama A, Onodera O
    • Organizer
      Neuroscience 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The absence of hypertension and the presence of psychiatric symptoms suggest a genetic disorder among patients suspected for hereditary cerebral small vessel disease2017

    • Author(s)
      Uemura M, Nozaki H, Sakai N, Onodera O
    • Organizer
      The 8th Korea Joint Stroke Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The prevalence estimates of HTRA1-associated cerebral small vessel disease2017

    • Author(s)
      Hiroaki Nozaki, Akihide Koyama, Masahiro Uemura, Taisuke Kato, Osamu Onodera
    • Organizer
      The 8th Korea-Japan Joint Stroke Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular analysis of mutant high-temperature requirement serine protease A1 identified in patients with familial cerebral small vessel disease2017

    • Author(s)
      Uemura M, Nozaki H, Kato T, Koyama A, Onodera O
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The prevalence estimates of HTRA1-associated cerebral small vessel disease2017

    • Author(s)
      Hiroaki Nozaki, Akihide Koyama, Masahiro Uemura, Taisuke Kato, Osamu Onodera
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 家族性脳小血管病患者で報告された変異型HTRA1蛋白質の機能解析2017

    • Author(s)
      上村昌寛, 野崎洋明, 加藤泰介, 小山哲秀, 小野寺理
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Distinct mechanisms of HTRA1 mutants in manifesting heterozygotes with CARASIL2017

    • Author(s)
      野崎 洋明, 加藤 泰介, 水田 依久子, 水野 敏樹, 西澤 正豊,小野寺 理
    • Organizer
      第114回日本内科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CARASIL症候性キャリアの一例2017

    • Author(s)
      野崎洋明, 伊藤 絢子, 阿部崇, 豊島靖子,佐藤晶, 橋立英樹, 五十嵐修一, 高橋均, 小野寺理, 柿田明美
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] セリンプロテアーゼHTRA1の機能欠損は、脳小血管病を引き起こす; Serine protease HTRA1 deficiency induces arteriopathy in cerebral small vessels2017

    • Author(s)
      Kato T, Sekine Y, Fujita N, Nozaki H, Hirokawa S, Sato T, Onodera O
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Protease activity analysis of mutant high-temperature requirement serine protease A1 identified in patients with familial cerebral small vessel disease2017

    • Author(s)
      Uemura M, Nozaki H, Kato T, Koyama A, Onodera O
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 家族性脳小血管病患者で同定された変異型HTRA1蛋白質のプロテアーゼ活性解析2017

    • Author(s)
      上村昌寛, 野崎洋明, 加藤泰介, 小山哲秀, 小野寺理
    • Organizer
      第47回新潟神経学夏季セミナー
    • Related Report
      2017 Annual Research Report
  • [Presentation] RVCL関連変異の細胞内局在についての検討.2017

    • Author(s)
      笠原杏子, 加藤泰介, 野崎洋明, 小山哲秀, 小野寺理.
    • Organizer
      第36回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Characteristic Brain Features of Manifesting Heterozygotes With Cerebral Autosomal Recessive Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.2017

    • Author(s)
      Masahiro Uemura, Hiroaki Nozaki, Yumi Sekine, , Osamu Onodera et al.
    • Organizer
      International stroke conference 2017
    • Place of Presentation
      Houston (USA)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distinct Molecular Mechanisms of Htra1 Mutants in Manifesting Heterozygotes With Carasil.2017

    • Author(s)
      Hiroaki Nozaki, Taisuke Kato, Megumi Nihonmatsu, Yohei Saito, Osamu Onodera, et al.
    • Organizer
      International stroke conference 2017
    • Place of Presentation
      Houston (USA)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2023-12-25  

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