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Development of next-generation therapy based on comprehensive molecular pathology of neurodegenerative diseases

Research Project

Project/Area Number 17H04196
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

Abe Koji  岡山大学, 医歯薬学総合研究科, 教授 (20212540)

Co-Investigator(Kenkyū-buntansha) 太田 康之  岡山大学, 大学病院, 講師 (20746854)
山下 徹  岡山大学, 医歯薬学総合研究科, 講師 (60644408)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords神経変性疾患 / ALS / アルツハイマー型認知症 / フリーラジカル / 酸化ストレス / 核細胞質輸送障害
Outline of Final Research Achievements

By using a AD model mouse with cerebral blood flow hypoperfusion established recently revealed that edaravone treatment can significantly improve motor and cognitive dysfunction. We also established novel ALS mice model that visualize oxidative stress, and found that the expression of oxidative stress in the spinal cord and lower limb muscles was enhanced early in the onset of ALS. Blood flow and glucose metabolism in the spinal cord of ALS patients were evaluated by PET examination, and it was observed that glucose metabolism was abnormally elevated in the ALS cervical spinal cord without increase in blood flow. Furthermore, as a result of exploratory research using a new peptideme analysis technology, 4 types of peptides specific to mild cognitive impairment (MCI) and Alzheimer's disease (AD) were found.

Academic Significance and Societal Importance of the Research Achievements

本研究は、神経変性疾患共通(普遍性のある)の分子病態解明のため、酸化ストレスと核細胞質輸送障害、蛋白ゲル化異常の相互関与に注目した挑戦的かつ総合的研究である。課題申請者らが発見したAsidanの病態も、欧米で特に多いC9orf72遺伝子異常との類似点から、神経変性疾患共通病態への関与に注目し解明を目指しており、本研究成果は国際的にも重要なインパクトを与えうる。本研究では神経変性疾患共通の分子病態解明および新規治療法開発につながる可能性があり、この課題研究から得られた成果は、将来的には神経変性疾患共通の根本的治療法の確立に道を開き、国際的にも波及効果の高い貢献をもたらすものと考えられる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (37 results)

All 2020 2019 2018 2017 Other

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 4 results) Presentation (22 results) (of which Int'l Joint Research: 9 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer's Disease by Peptidome Technology.2020

    • Author(s)
      Abe K, Shang J, Shi X, Yamashita T, Hishikawa N, Takemoto M, Morihara R, Nakano Y, Ohta Y, Deguchi K, Ikeda M, Ikeda Y, Okamoto K, Shoji M, Takatama M, Kojo M, Kuroda T, Ono K, Kimura N, Matsubara E, Osakada Y, Wakutani Y, Takao Y, Higashi Y, Asada K, Senga T, Lee LJ, Tanaka K
    • Journal Title

      J Alzheimers Dis.

      Volume: 73(1) Issue: 1 Pages: 217-227

    • DOI

      10.3233/jad-191016

    • NAID

      120006949464

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical and Pathological Benefits of Edaravone for Alzheimer’s Disease with Chronic Cerebral Hypoperfusion in a Novel Mouse Model2019

    • Author(s)
      Feng Tian、Yamashita Toru、Shang Jingwei、Shi Xiaowen、Nakano Yumiko、Morihara Ryuta、Tsunoda Keiichiro、Nomura Emi、Sasaki Ryo、Tadokoro Koh、Matsumoto Namiko、Hishikawa Nozomi、Ohta Yasuyuki、Abe Koji
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 71 Issue: 1 Pages: 327-339

    • DOI

      10.3233/jad-190369

    • NAID

      120006776434

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imaging Hypoxic Stress and the Treatment of Amyotrophic Lateral Sclerosis with Dimethyloxalylglycine in a Mice Model2019

    • Author(s)
      Nomura Emi、Ohta Yasuyuki、Tadokoro Koh、Shang Jingwei、Feng Tian、Liu Xia、Shi Xiaowen、Matsumoto Namiko、Sasaki Ryo、Tsunoda Keiichiro、Sato Kota、Takemoto Mami、Hishikawa Nozomi、Yamashita Toru、Kuchimaru Takahiro、Kizaka-Kondoh Shinae、Abe Koji
    • Journal Title

      Neuroscience

      Volume: 415 Pages: 31-43

    • DOI

      10.1016/j.neuroscience.2019.06.025

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion2019

    • Author(s)
      Liu Xia、Yamashita Toru、Shang Jingwei、Shi Xiaowen、Morihara Ryuta、Huang Yong、Sato Kota、Takemoto Mami、Hishikawa Nozomi、Ohta Yasuyuki、Abe Koji
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 28 Issue: 10 Pages: 104310-104310

    • DOI

      10.1016/j.jstrokecerebrovasdis.2019.104310

    • NAID

      120006885619

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic cerebral hypoperfusion alters amyloid-β transport related proteins in the cortical blood vessels of Alzheimer’s disease model mouse2019

    • Author(s)
      Shang Jingwei、Yamashita Toru、Tian Feng、Li Xianghong、Liu Xia、Shi Xiaowen、Nakano Yumiko、Tsunoda Keiichiro、Nomura Emi、Sasaki Ryo、Tadokoro Koh、Sato Kota、Takemoto Mami、Hishikawa Nozomi、Ohta Yasuyuki、Abe Koji
    • Journal Title

      Brain Research

      Volume: 1723 Pages: 146379-146379

    • DOI

      10.1016/j.brainres.2019.146379

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic Cerebral Hypoperfusion Activates the Coagulation and Complement Cascades in Alzheimer's Disease Mice2019

    • Author(s)
      Shi Xiaowen、Ohta Yasuyuki、Liu Xia、Shang Jingwei、Morihara Ryuta、Nakano Yumiko、Feng Tian、Huang Yong、Sato Kota、Takemoto Mami、Hishikawa Nozomi、Yamashita Toru、Abe Koji
    • Journal Title

      Neuroscience

      Volume: 416 Pages: 126-136

    • DOI

      10.1016/j.neuroscience.2019.07.050

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute Anti-Inflammatory Markers ITIH4 and AHSG in Mice Brain of a Novel Alzheimer’s Disease Model2019

    • Author(s)
      Shi Xiaowen、Ohta Yasuyuki、Liu Xia、Shang Jingwei、Morihara Ryuta、Nakano Yumiko、Feng Tian、Huang Yong、Sato Kota、Takemoto Mami、Hishikawa Nozomi、Yamashita Toru、Abe Koji
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 68 Issue: 4 Pages: 1667-1675

    • DOI

      10.3233/jad-181218

    • NAID

      120006839252

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study2019

    • Author(s)
      Tadokoro Koh、Morihara Ryuta、Abe Koji et al.,
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: 71 Issue: 3 Pages: 1063-1069

    • DOI

      10.3233/jad-190644

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhanced oxidative stress and the treatment by edaravone in mice model of amyotrophic lateral sclerosis.2018

    • Author(s)
      Ohta Y, Nomura E, Shang J, Feng T, Huang Y, Liu X, Shi X, Nakano Y, Hishikawa N, Sato K, Takemoto M, Yamashita T, Abe K.
    • Journal Title

      J Neurosci Res.

      Volume: Epub ahead of print Issue: 5 Pages: 607-619

    • DOI

      10.1002/jnr.24368

    • NAID

      120006776453

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detecting spinal pyramidal tract of amyotrophic lateral sclerosis patients with diffusion tensor tractography.2017

    • Author(s)
      Fukui Y, Hishikawa N, Sato K, Nakano Y, Morihara R, Shang J, Takemoto M, Ohta Y, Yamashita T, Abe K.
    • Journal Title

      Neurosci Res.

      Volume: Epub ahead of print Pages: 58-63

    • DOI

      10.1016/j.neures.2017.11.005

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Flow-metabolism uncoupling in the cervical spinal cord of ALS patients.2017

    • Author(s)
      Yamashita T, Hatakeyama T, Sato K, Fukui Y, Hishikawa N, Ohta Y, Nishiyama Y, Kawai N, Tamiya T, Abe K.
    • Journal Title

      Neurol Sci.

      Volume: 38 Issue: 4 Pages: 659-665

    • DOI

      10.1007/s10072-017-2823-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Potential multisystem degeneration in Asidan patients.2017

    • Author(s)
      Ohta Y, Yamashita T, Hishikawa N, Sato K, Matsuzono K, Tsunoda K, Hatanaka N, Takemoto M, Takemi T, Takamatsu K, Abe K
    • Journal Title

      J Neurol Sci.

      Volume: 373 Pages: 216-222

    • DOI

      10.1016/j.jns.2017.01.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Behavioral and affective features of amyotrophic lateral sclerosis patients.2017

    • Author(s)
      Ohta Y, Sato K, Takemoto M, Takahashi Y, Morihara R, Nakano Y, Tsunoda K, Nomura E, Hishikawa N, Yamashita T, Abe K
    • Journal Title

      J Neurol Sci.

      Volume: 381 Pages: 119-125

    • DOI

      10.1016/j.jns.2017.08.024

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aberrant distributions of nuclear pore complex proteins in ALS mice and ALS patients.2017

    • Author(s)
      Shang J, Yamashita T, Nakano Y, Morihara R, Li X, Feng T, Liu X, Huang Y, Fukui Y, Hishikawa N, Ohta Y, Abe K
    • Journal Title

      Neuroscience.

      Volume: 350 Pages: 158-168

    • DOI

      10.1016/j.neuroscience.2017.03.024

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Therapeutic benefits of edaravone for enhanced oxidative stress in mice model of amyotrophic lateral sclerosis.2019

    • Author(s)
      Ohta Y, Nomura E, Shang J, Feng T, Liu X, Shi X, Hishikawa N, Takemoto M, Yamashita T, Abe K
    • Organizer
      BRAIN & BRAIN PET 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Reduction of intracerebral hemorrhage by rivaroxaban after tPA thrombolysis is associated with downregulation of PAR-1 and PAR-22019

    • Author(s)
      Yamashita T, Morihara R, Kono S, Shang J, Nakano Y, Sato K, Hishikawa N, Ohta Y, Heitmeier S, Perzborn E, Abe K
    • Organizer
      BRAIN & BRAIN PET 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vivo direct reprogramming of glial linage to mature neurons after cerebral ischemia2019

    • Author(s)
      Yamashita T, Shang J, Nakano Y, Morihara R, Sato K, Takemoto M, Hishikawa N, Ohta Y, Abe K
    • Organizer
      Asia Pacific Stroke Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Animal models of vascular cognitive impairment2019

    • Author(s)
      Yamashita T, Abe K
    • Organizer
      Asia Pacific Stroke Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Therapeutic effects of edaravone for enhanced oxidative stress in amyotrophic lateral sclerosis mice2019

    • Author(s)
      Ohta Y, Nomura E, Shang J, Feng T, Nakano Y, Hishikawa N, Sato K, Takemoto M, Yamashita T, Omote Y, Abe K
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ALS幹細胞治療の新展開2019

    • Author(s)
      山下徹、阿部康二
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] パーキンソン病とレビー小体型認知症の検査所見やmicrobleeds出現頻度の違いについて2019

    • Author(s)
      武本麻美、佐藤恒太、太田康之、山下徹、菱川望、阿部康二
    • Organizer
      第60回日本神経学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規遺伝性疾患 Asidan (SCA36)におけるDAT scanの特徴2019

    • Author(s)
      太田康之、山下徹、菱川望、佐藤恒太、角田慶一郎、幡中典子、武本麻美、商敬偉、阿部康二
    • Organizer
      第42回日本脳神経CI学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MRI・DAT SPECTでパーキンソニズムの左右差に合致した異常所見を認めた日本脳炎の一例2019

    • Author(s)
      田所功、太田康之、佐藤恒太、前木孝洋、武本麻美、菱川望、山下徹、田島茂、林昌宏、阿部康二
    • Organizer
      第42回日本脳神経CI学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規酸化ストレスイメージングによるALSへのエダラボン治療効果の検討2019

    • Author(s)
      太田康之、野村恵美、山下徹、馮田、佐藤恒太、武本麻美、菱川望、表芳夫、阿部康二
    • Organizer
      第37回日本神経治療学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Clinical predictors of Alzheimer’s disease progression2019

    • Author(s)
      Hishikawa N, Omote Y, Shang J, Takemoto M, Yamashita T, Ohta Y, Abe K
    • Organizer
      第38回 日本認知症学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞移植による神経再生療法2019

    • Author(s)
      山下徹、阿部康二
    • Organizer
      第10回日本脳血管・認知症学会総会(Vas-Cog Japan 2019)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Flow-metabolism uncoupling in the cervical spinal cord of ALS patients.2018

    • Author(s)
      Yamashita T, Nakano Y, Morihara R, Shang J, Sato K, Hishikawa N, Ohta Y, Abe K
    • Organizer
      The 11th Pan Pacific Symposium on Stem Cells and Cancer Research
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical features of Asidan patients with DWEP.2018

    • Author(s)
      Ohta Y, Yamashita T, Hishikawa N, Sato K, Tsunoda K, Hatanaka N, Takemoto M, Abe K
    • Organizer
      The 2nd Asidan/SCA36 international symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical characterization of Asidan in Japan.2018

    • Author(s)
      Yamashita T, Ohta Y, Abe K
    • Organizer
      The 2nd Asidan/SCA36 international symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The pathological role of P413L variant chromogranin B as disease modifier in female amyotrophic lateral sclerosis.2018

    • Author(s)
      Ohta Y, Soucy G, Phaneuf D, Audet JN, Gros-Louis F, Yamashita T, Sato K, Takemoto M, Hishikawa N, Julien JP, Abe K
    • Organizer
      第59回日本神経学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ALSモデルマウス骨格筋における酸化ストレスの関与2018

    • Author(s)
      太田康之、野村恵美、商敬偉、山下徹、馮田、黄永、佐藤恒太、武本麻美、菱川望、阿部康二
    • Organizer
      日本筋学会第4回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Chronic Cerebral Hypoperfusion Accelerates Alzheimer’s Disease Pathology with Cerebrovascular Remodeling in a Novel Mouse Model2017

    • Author(s)
      Yamashita T, Zhai Y, Nakano Y, Morihara R, Shang J, Abe K
    • Organizer
      BRAIN 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ALS患者頚髄では糖代謝と血流のuncouplingが起きている2017

    • Author(s)
      山下徹、畠山哲宗、佐藤恒太、中野由美子、森原隆太、商敬偉、福井祐介、菱川望、太田康之、西山佳宏、河井信行、田宮隆、阿部康二
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The role of variant chromogranin B as disease modifier in Japanese female amyotrophic lateral sclerosis.2017

    • Author(s)
      Ohta Y, Soucy G, Phaneuf D, Audet JN, Gros-Louis F, Yamashita T, Sato K, Takemoto M, Hishikawa N, Julien JP, Abe K
    • Organizer
      XXIII World Congress of Neurology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 虚血負荷によるTDP43、FUS/TLSの発現亢進と神経細胞保護効果の関係2017

    • Author(s)
      中野由美子、孫淼、山下徹、森原隆太、佐藤恒太、菱川望、太田康之、阿部康二
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新しいSCA/ALS crossroad mutation AsidanのDWEP現象2017

    • Author(s)
      太田康之、山下徹、佐藤恒太、幡中典子、角田慶一郎、武本麻美、菱川望、阿部康二
    • Organizer
      第5回日本難病医療ネットワーク学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 少量の血液から認知症リスクが診断可能に!認知症リスクの指標となる血中ペプチドバイオマーカーを発見

    • URL

      https://www.okayama-u.ac.jp/tp/release/release_id699.html

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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