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Elucidation of the Pathology of Synucleinopathies and Development of New Therapies Focused on Serum Alpha-Synuclein Seeds

Research Project

Project/Area Number 21K07424
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionJuntendo University

Principal Investigator

Taku Hatano  順天堂大学, 大学院医学研究科, 准教授 (60338390)

Co-Investigator(Kenkyū-buntansha) 上野 真一  順天堂大学, 医学部, 助教 (40875944)
奥住 文美  順天堂大学, 医学部, 准教授 (90826075)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsα-シヌクレイン / パーキンソン病 / 多系統萎縮症 / IP/RT-QuIC / シヌクレイノパチー / αシヌクレイン / 血漿交換療法 / バイオマーカー
Outline of Research at the Start

申請者はパーキンソン病や多系統萎縮症といったαシヌクレインが凝集する神経変性疾患の血液から、凝集の起点となるαシヌクレインシードを発見した。本研究課題では血液αシヌクレインシードを診断バイオマーカーとして確立し、さらにこれを除去することによる疾患修飾療法の開発を目指すことを目的とする。除去について血漿交換療法のマウスモデルで有用性を検討する。本研究を遂行することで、パーキンソン病や多系統萎縮症に対して治療方法が確立できれば患者の生活の質及び日常生活動作の改善が見込まれる。

Outline of Final Research Achievements

We have established a new diagnostic technique called IP/RT-QuIC, which identifies pathogenic alpha-synuclein seeds from serum. This method has successfully differentiated patients with Parkinson's disease from healthy controls with high accuracy. While the precision for diagnosing patients with multiple system atrophy was slightly lower, there were more positive cases than in the controls. We also collaborated with Luxenberg, and their double-blind cohort successfully differentiated from Parkinson's disease to control. Thus, we developed our technique as a valuable detection of diagnostic marker. These findings have been published in sNature Medicine. In addition, using the RT-QuIC method, seeds were identified from whole-body organs in pathologically diagnosed cases. Research has also been conducted on a mouse model to track the distribution of alpha-synuclein seeds.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した血清ASシードの同定はシヌクレイノパチーをバイオロジカルに診断する重要な手がかりとなった。さらに、得られた凝集体の構造がシヌクレイノパチーにおいて異なることは、鑑別診断に有用であることに加えて、病態メカニズムの解明にも一石を投じる革新的な研究である。また、血清にASシードが存在することの発見により、全身臓器にASシードが存在することが予想され、実際に病理学的に確認している点で学術的に重要な研究である。さらに血清や全身のASシードをターゲットとした治療法である血漿交換療法が確立されれば、新規疾患修飾治療として社会的意義が大きい。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (31 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] Luxembourg Institute of Health (LIH)(ルクセンブルク)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Luxemburg National Center(ルクセンブルク)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Free-water diffusion magnetic resonance imaging under selegiline treatment in Parkinson's disease2024

    • Author(s)
      Takeshige-Amano Haruka、Hatano Taku、Kamagata Koji、Andica Christina、Ogawa Takashi、Shindo Atsuhiko、Uchida Wataru、Sako Wataru、Saiki Shinji、Shimo Yasushi、Oyama Genko、Umemura Atsushi、Ito Masanobu、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 457 Pages: 122883-122883

    • DOI

      10.1016/j.jns.2024.122883

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Propagative α-synuclein seeds as serum biomarkers for synucleinopathies.2023

    • Author(s)
      Ayami Okuzumi Taku Hatano Gen Matsumoto Nobutaka Hattori et al
    • Journal Title

      Nature medicine

      Volume: 29 Issue: 6 Pages: 1448-1455

    • DOI

      10.1038/s41591-023-02358-9

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Idiopathic rapid eye movement sleep behavior disorder in Japan: An observational study2022

    • Author(s)
      Nishikawa N、Murata M、Hatano T、Mukai Y、Saitoh Y、Sakamoto T、Hanakawa T、Kamei Y、Tachimori H、Hatano K、Matsuda H、Taruno Y、Sawamoto N、Kajiyama Y、Ikenaka K、Kawabata K、Nakamura T、Iwaki H、Kadotani H、Sumi Y、Inoue Y、Hayashi T、Ikeuchi T、Shimo Y、Mochizuki H、Watanabe H、Hattori N、Takahashi Y、Takahashi R
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 103 Pages: 129

    • DOI

      10.1016/j.parkreldis.2022.08.011

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] α-Synuclein V15A variant in familial Parkinson's disease exhibits a weaker lipid-binding property.2022

    • Author(s)
      Daida K, Shimonaka S, Shiba-Fukushima K, Ogata J, Yoshino H, Okuzumi A, Hatano T, Motoi Y, Hirunagi T, Katsuno M, Shindou H, Funayama M, Nishioka K, Hattori N, Imai Y.
    • Journal Title

      Mov Disord.

      Volume: 37 Issue: 10 Pages: 2075-2085

    • DOI

      10.1002/mds.29162

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systematic analysis of the molecular mechanisms mediated by coffee in Parkinson’s disease based on network pharmacology approach2021

    • Author(s)
      Li Fangjun、Hatano Taku、Hattori Nobutaka
    • Journal Title

      Journal of Functional Foods

      Volume: 87 Pages: 104764-104764

    • DOI

      10.1016/j.jff.2021.104764

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comorbid alpha synucleinopathies in idiopathic normal pressure hydrocephalus2021

    • Author(s)
      Sakurai Anri、Tsunemi Taiji、Ishiguro Yuta、Okuzumi Ayami、Hatano Taku、Hattori Nobutaka
    • Journal Title

      Journal of Neurology

      Volume: 269 Issue: 4 Pages: 2022-2029

    • DOI

      10.1007/s00415-021-10778-1

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] White matter alterations in Parkinson's disease with levodopa-induced dyskinesia2021

    • Author(s)
      Ogawa Takashi、Hatano Taku、Kamagata Koji、Andica Christina、Takeshige-Amano Haruka、Uchida Wataru、Saito Yuya、Shimo Yasushi、Oyama Genko、Umemura Atsushi、Iwamuro Hirokazu、Ito Masanobu、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
    • Journal Title

      Parkinsonism & Related Disorders

      Volume: 90 Pages: 8-14

    • DOI

      10.1016/j.parkreldis.2021.07.021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fiber-specific white matter alterations in early-stage tremor-dominant Parkinson’s disease2021

    • Author(s)
      Andica Christina、Kamagata Koji、Saito Yuya、Uchida Wataru、Fujita Shohei、Hagiwara Akifumi、Akashi Toshiaki、Wada Akihiko、Ogawa Takashi、Hatano Taku、Hattori Nobutaka、Aoki Shigeki
    • Journal Title

      npj Parkinson's Disease

      Volume: 7 Issue: 1 Pages: 1-8

    • DOI

      10.1038/s41531-021-00197-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Orthostatic Hypotension With Cerebral Atrophy in Patients With Lewy Body Disorders2021

    • Author(s)
      Pilotto A、Hatano T(23/30)et al
    • Journal Title

      Neurology

      Volume: 97 Issue: 8

    • DOI

      10.1212/wnl.0000000000012342

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diffusion MRI Captures White Matter Microstructure Alterations in PRKN Disease2021

    • Author(s)
      Koinuma Takahiro、Hatano Taku、Kamagata Koji、Andica Christina、Mori Akio、Ogawa Takashi、Takeshige-Amano Haruka、Uchida Wataru、Saiki Shinji、Okuzumi Ayami、Ueno Shin-Ichi、Oji Yutaka、Saito Yuya、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
    • Journal Title

      Journal of Parkinson's Disease

      Volume: - Issue: 3 Pages: 1-15

    • DOI

      10.3233/jpd-202495

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] White matter and nigral alterations in multiple system atrophy-parkinsonian type2021

    • Author(s)
      Ogawa Takashi、Hatano Taku、Kamagata Koji、Andica Christina、Takeshige-Amano Haruka、Uchida Wataru、Kamiyama Daiki、Shimo Yasushi、Oyama Genko、Umemura Atsushi、Iwamuro Hirokazu、Ito Masanobu、Hori Masaaki、Aoki Shigeki、Hattori Nobutaka
    • Journal Title

      npj Parkinson's Disease

      Volume: 7 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41531-021-00236-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Challenges and Future Prospects for Diagnostic Imaging and Biomarkers of Parkinson's Disease and Atypical Parkinsonism2023

    • Author(s)
      Hatano T, Okuzumi A, Takeshige-Amano H, Ogawa T, Hattori N
    • Organizer
      第64回日本神経学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] α-synuclein:Biomarker of Synucleinopathy2023

    • Author(s)
      Hatano T, Okuzumi A, Hattori N.
    • Organizer
      MDS-AOS Basic Summer School
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Pathogenesis of α-synucleinopathy2023

    • Author(s)
      Hatanot T, Okuzumi A, Hattori N.
    • Organizer
      UK-JP Neuroscience Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Propagative α-synuclein seeds as serum biomarkers in synucleinopathies2023

    • Author(s)
      Hatano T, Okuzumi A, Hattori N
    • Organizer
      18th annual GEoPD meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Alpha Synuclein Aggregation and Propagation2023

    • Author(s)
      Hatano T, Okuzumi A, Hattori N.
    • Organizer
      10th Singapore International Parkinson Disease and Movement Disorders Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of seral disease-specific alpha-synuclein seeds using IP-RT-QuIC.2022

    • Author(s)
      Okuzumi A, Hatano T, Matsumoto G, Nukina N, Hattori N.
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Analysis of α-synuclein aggregation and proteomics in Parkinson’s disease.2022

    • Author(s)
      Ueno SI, Hatano T, Okuzumi A, Oda Y, Hattori N.
    • Organizer
      第63回日本神経学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Mechanisms of α-synuclein aggregation and potential treatment strategy for PD2022

    • Author(s)
      Taku Hatano, Akio Mori, Yutaka Oji, Ayami Okuzumi and Nobutaka Hattori
    • Organizer
      RIKEN Symposium ~ Mechanistic Insights into Neurodegenerative Disorders ~
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] The pathomechanisms of Levodopa-Induced Dyskinesia in Parkinson’s disease.2022

    • Author(s)
      Taku Hatano, Takashi Ogawa, Nobutaka Hattori
    • Organizer
      第95回日本薬理学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Lipid Metabolism and α-synuclein aggregation2021

    • Author(s)
      Taku Hatano and Nobutaka Hattori
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 腸管からパーキンソン病を考える2021

    • Author(s)
      波田野琢、服部信孝
    • Organizer
      第74回日本自律神経学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 生体内のαシヌクレインタンパク質が見たい!2021

    • Author(s)
      4.波田野琢、服部信孝
    • Organizer
      第61回日本核医学会学術総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Searching for novel biomarkers in Parkinson’s disease.2021

    • Author(s)
      Taku Hatano, Ayami Okuzumi, and Nobutaka Hattori
    • Organizer
      The 2021 Annual meeting of the Korean Society of Neurodegenerative Disease (KSND) 30th
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Updates in Neuroimaging for Parkinson Disease and Related Disorders2021

    • Author(s)
      Taku Hatano, Nobutaka Hattori
    • Organizer
      9th Singapore International Parkinson Disease and Movement Disorders Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Metabolite Biomarkers Parkinson Disease and Parkinsonism2021

    • Author(s)
      Taku Hatano, Nobutaka Hattori
    • Organizer
      9th Singapore International Parkinson Disease and Movement Disorders Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanisms of α-synuclein aggregation and potential treatment strategy for PD2021

    • Author(s)
      Taku Hatano, Nobutaka Hattori
    • Organizer
      MDS-AOS Basic Science Summer School
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] 順天堂大学脳神経内科ではこうしている 最新パーキンソン病診療2021

    • Author(s)
      波田野琢 (服部信孝編)
    • Total Pages
      224
    • Publisher
      日本醫事新報社
    • Related Report
      2021 Research-status Report
  • [Remarks] NCER-PD

    • URL

      https://parkinson.lu

    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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