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Novel therapeutic strategy for amyotrophic lateral sclerosis targeting calretinin and monocyte chemoattractant protein-1

Research Project

Project/Area Number 25461317
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionKyushu University

Principal Investigator

HAYASHI SHINTARO  九州大学, 医学(系)研究科(研究院), 研究員 (90312876)

Co-Investigator(Kenkyū-buntansha) OHYAGI YASUMASA  愛媛大学, 医学系研究科, 教授 (30301336)
TATEISHI TAKAHISA  九州大学, 医学研究院, 共同研究員 (50423546)
KAWAMURA NOBUTOSHI  九州大学, 医学研究院, 共同研究員 (00432930)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords筋萎縮性側索硬化症 / カルレチニン / 単球走化性蛋白質1 / ミクログリア / マクロファージ / TDP-43 / 脊髄前側索 / カルシウム結合蛋白 / 運動ニューロン / 孤発性筋萎縮性側索硬化症 / 樹状細胞 / 単球走化性蛋白1
Outline of Final Research Achievements

We examined relationships between massive microglia/macrophage (Mi/MΦ) infiltrations in the anterolateral funiculus of amyotrophic lateral sclerosis (ALS) spinal cord and TDP-43 pathology, calretinin (CR, calcium-binding protein), and CCL2 (monocyte chemoattractant protein-1). The results showed that among the Mi/MΦ with various morphologies, the numbers of Mi/MΦ with foamy appearance had a positive correlation with amount of motor neurons with TDP-43 pathology in ALS patients. It was also revealed morphologically that CCL2, elevated in the patient's cerebrospinal fluid, might be derived from the astrocytes. Although, distributions of Mi/MΦ in ALS spinal cord are similar to those of CR-immunoreactive axons in normal human spinal cord, administration of anti-CR antibodies to ALS mouse model (G93A) or CR peptide to normal rat indicated no pathogenicity of CR.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 1 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Ectopic germinoma involving multiple midline and paramedian structures outside the pineal gland or hypophyseal region of the brain prior to tumor development2015

    • Author(s)
      Hayashi S, Okamoto K
    • Journal Title

      J Neurol Sci

      Volume: 358 Pages: 512-514

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A case of chronic progressive motor-dominant multiple mononeuritis associated with primary Sjögren’s syndrome2015

    • Author(s)
      Saitoh BY, Hayashi S, Kamada T, Murai H, Omoto M, Kira J
    • Journal Title

      Rinsho Shinkeigaku

      Volume: 55 Issue: 10 Pages: 753-758

    • DOI

      10.5692/clinicalneurol.cn-000748

    • NAID

      130005103331

    • ISSN
      0009-918X, 1882-0654
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome presenting with hypertrophic pachymeningitis2015

    • Author(s)
      Shiraishi W, Hayashi S, Iwanaga Y, Murai H, Yamamoto A, Kira J
    • Journal Title

      J Neurol Sci

      Volume: 349 Issue: 1-2 Pages: 229-231

    • DOI

      10.1016/j.jns.2014.12.020

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model.2014

    • Author(s)
      Cui Y and Masaki K et al
    • Journal Title

      J Neuroinflammation

      Volume: 11 Issue: 1 Pages: 42-42

    • DOI

      10.1186/1742-2094-11-42

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of adult-onset reducing body myopathy presenting a novel clinical feature, asymmetrical involvement of the sternocleidomastoid and trapezius muscles2014

    • Author(s)
      Fujii T, Hayashi S, Kawamura N, Higuchi MA, Tsugawa J, Ohyagi Y, Hayashi YK, Nishino I, Kira J
    • Journal Title

      J Neurol Sci

      Volume: 343 Pages: 206-210

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased CCR2 and CD62L expression on peripheral blood classical monocytes in amyotrophic lateral sclerosis2014

    • Author(s)
      Yi Wen Cui, Yuji Kawano, Ryo Yamasaki, Nan Shi, Katsuhisa Masaki, Noriko Isobe, Tomomi Yonekawa, Takuya Matsushita, Takahisa Tateishi, Shintaro Hayashi, and Jun-ichi Kira
    • Journal Title

      Clinical and Experimental Neuroimmunology

      Volume: in press

    • Related Report
      2013 Research-status Report
  • [Journal Article] Loss of calretinin- and parvalbumin-immunoreactive axons in anterolateral columns beyond the corticospinal tracts of amyotrophic lateral sclerosis spinal cords2013

    • Author(s)
      Shintaro Hayashi, Masakuni Amari, Koichi Okamoto
    • Journal Title

      Journal of the Neurological Sciences

      Volume: 331 Issue: 1-2 Pages: 61-66

    • DOI

      10.1016/j.jns.2013.05.008

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired cytoplastic-nuclear transport of hypoxia-inducible factor-1αin amgotrophic lateral sclerosis.2013

    • Author(s)
      Kira J et al
    • Journal Title

      Brain Pathol

      Volume: - Issue: 5 Pages: 534-546

    • DOI

      10.1111/bpa.12040

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] A certain morphology of activated microglia, which correlates with TDP-43 pathology in ALS spinal cord2015

    • Author(s)
      Shintaro Hayashi, Ryo Yamasaki, Katsuhisa Masaki, Hiroyuki Murai, Koichi Okamoto, Jun-ichi Kira
    • Organizer
      26th International Symposium on ALS/MND
    • Place of Presentation
      JW Mariott Grand Lakes, Orland (USA)
    • Year and Date
      2015-12-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 活性化ミクログリアの形態差と脊髄内局在差がTDP-43病理形成 に与える影響の解析2015

    • Author(s)
      林信太郎、眞崎勝久、山崎亮、村井弘之、岡本幸市、吉良潤一
    • Organizer
      第27回日本神経免疫学会学術集会
    • Place of Presentation
      長良川国際会議場(岐阜)
    • Year and Date
      2015-09-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Impact of activated microglial morphologies on motor neuron degeneration in ALS spinal cord2015

    • Author(s)
      Hayashi S, Yamasaki R, Masaki K, Murai H, Okamoto K, Kira J
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      朱鷺メッセ(新潟)
    • Year and Date
      2015-05-20
    • Related Report
      2015 Annual Research Report
  • [Presentation] Morphological evidences of glial inflammation that confer spinal white matter degeneration of sporadic amyotrophic lateral sclerosis2014

    • Author(s)
      Hayashi S, Yamasaki R, Masaki K, Murai H, Okamoto K, Kira J
    • Organizer
      25th International symposium on ALS-MND
    • Place of Presentation
      ブリュッセル (ベルギー)
    • Year and Date
      2014-12-05 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 筋萎縮性側索硬化症におけるグリア性炎症初期像の同定:発症早期組織と末期組織を用いた免疫病理学的検討2014

    • Author(s)
      林信太郎、山崎亮、眞崎勝久、村井弘之、岡本幸市、吉良潤一
    • Organizer
      第26回日本神経免疫学会学術集会
    • Place of Presentation
      金沢歌劇座(金沢)
    • Year and Date
      2014-09-04 – 2014-09-06
    • Related Report
      2014 Research-status Report
  • [Presentation] 免疫細胞群からみた孤発性筋萎縮性側索硬化症の脊髄白質変性機序の再検討2014

    • Author(s)
      林信太郎、山崎亮、眞崎勝久、村井弘之、大八木保政、岡本幸市、吉良潤一
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] グリア性炎症からみた筋萎縮性側索硬化症の脊髄白質変性に関する形態学的検証2013

    • Author(s)
      林信太郎、眞崎勝久、崔訳文、長柄祐子、大八木保政、岡本幸市、吉良潤一
    • Organizer
      第54回日本神経学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 孤発性筋萎縮性側索硬化症の脊髄白質に浸潤する免疫細胞群の特徴: 免疫組織化学的解析2013

    • Author(s)
      林信太郎、眞崎勝久、山崎亮、村井弘之、大八木保政、岡本幸市、吉良潤一
    • Organizer
      第25回日本神経免疫学会学術集会
    • Place of Presentation
      下関
    • Related Report
      2013 Research-status Report
  • [Presentation] TDP-43(A315T) tgマウスの脊髄運動ニューロンにおける核細胞質間輸送障害の解析2013

    • Author(s)
      長柄祐子、林信太郎、山崎亮、大八木保政、吉良潤一
    • Organizer
      第54回日本神経学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] ALSマウスモデルにおける病態進行に伴うコネキシン蛋白群の変動2013

    • Author(s)
      崔訳文、眞崎勝久、山崎亮、林信太郎、長柄祐子、河村真実、今村志穂子、佐藤眞也、吉良潤一
    • Organizer
      第25回日本神経免疫学会学術集会
    • Place of Presentation
      下関
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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