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A nasal injection of adiponectin: a novel therapeutic strategy against neurodegenerative disease

Research Project

Project/Area Number 25640030
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Nerve anatomy/Neuropathology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

HASHIMOTO Makoto  公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野., 副参事研究員 (50189502)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsαシヌクレイン / βシヌクレイン / パーキンソン病 / アルツハイマー病 / アディポネクチン / レビー小体型認知症 / 神経変性疾患 / 鼻腔投与 / アディポネクチン(APN) / αシヌクレイン(αS) / パーキンソン病(PD) / トランスジェニック(tg)マウス / シヌクレイン / 糖尿病
Outline of Final Research Achievements

Neurodegenerative diseases are associated with metabolic disorders, but the mechanisms are still unclear. To investigate possible roles of adiponectin (APN), the anti-diabetes protein, in the pathogenesis of α-synucleinopathies, we investigated autopsy brain of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and analyzed the effects of APN in cellular and in mouse models of α-synucleinopathies.In autopsy brains, APN was localized in Lewy bodies derived from PD and DLB. In neuronal cells expressing α-synuclein (αS), aggregation of αS was suppressed by treatment with recombinant APN in an AdipoRI-AMP kinase pathway-dependent manner. Concomitantly, phosphorylation and release of αS were significantly decreased by APN. In αS transgenic mice, both histopathology and movement disorder were significantly improved by intra nasal treatment with globular APN. Collectively, APN could possess a therapeutic potential against α-synucleinopathies.

Report

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

    (20 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Possible Involvement of Adiponectin, the Anti-Diabetes Molecule, in the Pathogenesis of Alzheimer’s Disease.2016

    • Author(s)
      Waragai M, Adame A, Trinh I, Sekiyama K, Takamatsu Y, Une K, Masliah E, Hashimoto M
    • Journal Title

      J Alzheimers Dis.

      Volume: in press Issue: 4 Pages: 1453-1459

    • DOI

      10.3233/jad-151116

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insight into the dissociation of behavior from histology in Synucleinopathies and in related neurodegenerative diseases2016

    • Author(s)
      Sekiyama K, Takamatsu Y, Koike W, Waragai M, Takenouchi T, Sugama S, Hashimoto M.
    • Journal Title

      Journal of Alzheimer's Disease

      Volume: in press Issue: 3 Pages: 831-841

    • DOI

      10.3233/jad-151015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Role of α- and β-Synucleins in the Axonal Pathology of Parkinson's Disease and Related Synucleinopathies.2015

    • Author(s)
      Sekigawa A, Takamatsu Y, Sekiyama K, Hashimoto M.
    • Journal Title

      Biomolecules.

      Volume: 5 Issue: 2 Pages: 1000-1011

    • DOI

      10.3390/biom5021000

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Disease-Modifying Effect of Adiponectin in Model of α-Synucleinopathie2014

    • Author(s)
      Sekiyama K, Waragai M, Akatsu H, Sugama S, Takenouchi T, Takamatsu Y, Fujita M, Sekigawa A, Rockenstein E, Inoue S, La Spada A, Masliah E, Hashimoto M
    • Journal Title

      Ann Clin Transl Neurol

      Volume: 1 Issue: 7 Pages: 479-489

    • DOI

      10.1002/acn3.77

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of genomics in translational research for Parkinson's disease.2014

    • Author(s)
      Sekiyama, K., Takamatsu, Y., Waragai, M., Hashimoto, M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 452 (2) Issue: 2 Pages: 226-235

    • DOI

      10.1016/j.bbrc.2014.06.028

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dual effects of beta-synuclein in the pathogenesis of Parkinson's disease2013

    • Author(s)
      Akio Sekigawa, Kazunai Sekiyama, Masayo Fujita, Yoshiki Takamatsu, Albert R. La Spada Eliezer Maslah, Makoto Hashimotoi
    • Journal Title

      Annals of Neurology

      Volume: 74 Pages: 306-306

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diversity of mitochondrial pathology in a mouse model of axonal degeneration in synucleinopathies2013

    • Author(s)
      Sekigawa A
    • Journal Title

      Oxid Med Cell Longev.

      Volume: 2013 Pages: 817807-817807

    • DOI

      10.1155/2013/817807

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biomarkers for the diagnosis and management of Parkinson's disease2013

    • Author(s)
      Waragai M, Sekiyama K, Fujita M, Tokuda T, Hashimoto M.
    • Journal Title

      Expert Opin Med Diagn.

      Volume: 1 Pages: 71-83

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] レビー小体型認知症で同定された2種類の変異型βシヌクレイン(P123H、V70M)は、ショウジョウバエ脳において異なるメカニズムで神経変性を引き起こす2015

    • Author(s)
      高松 芳樹、関山 一成、井上 聡、本多 芳子、児玉 亨、橋本 款
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際展示場(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Disease Modifying Effect of Adiponectin in a Model of α-Synucleinopathies in Vitro and in Vivo.2015

    • Author(s)
      Masaaki Waragai, Kazunari Sekiyama, Yoshiki Takamatsu, Masayo Fujita, Akio Sekigawa, Naomichi Iwai, Edward Rockenstein, Satoshi Inoue, Albert R. La Spada, Elizer Masliah, Makoto Hashimoto
    • Organizer
      Alzheimer's Association International Conference (AAIC2015)
    • Place of Presentation
      Washington D.C., USA
    • Year and Date
      2015-07-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗糖尿病因子;アディポネクチンを用いたパーキンソン病の発症前治療法の可能性2015

    • Author(s)
      橋本 款
    • Organizer
      第12回 RCGM フロンティア国際シンポジウム、サテライトミーティング(招待講演)
    • Place of Presentation
      埼玉医科大学ゲノムセンター、埼玉県入間郡
    • Year and Date
      2015-02-13
    • Related Report
      2014 Research-status Report
  • [Presentation] アディポネクチンはα-シヌクレイノパチー細胞モデルのインスリンシグナルを亢進し神経変性の病態を改善する2014

    • Author(s)
      関山 一成, 高松 芳樹, 橋本 款
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜、神奈川県横浜市
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] レビー小体型認知症て同定された変異型β シヌクレイン(P123H, V70M) を導入した ショウジョウバエの解析2013

    • Author(s)
      高松芳樹、関川明生、堀内純ニ郎、関山一成、藤田雅代、児玉亨、齊藤実、橋本款
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] シヌクレイノパチー病態におけるアテ?ィホ?ネクチンの治療効果について2013

    • Author(s)
      関山一成、藤田雅代、高松芳樹、橋本款
    • Organizer
      第36回日本分子生物学会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] The anti-diabetic hormone, adiponectin, has protective effect on the pathogenesis of in vitro and in vivo models of α-synucleinopathies.2013

    • Author(s)
      Sekiyama K, Fujita M, Sekigawa A, Takamatsu Y, Hashimoto M
    • Organizer
      Neuroscinence 2013
    • Place of Presentation
      San Diego USA
    • Related Report
      2013 Research-status Report
  • [Book] 遺伝子治療・診断の最先端技術と新しい医薬品・診断薬の開発2014

    • Author(s)
      高松芳樹、関山一成、橋本款
    • Publisher
      技術情報協会
    • Related Report
      2013 Research-status Report
  • [Book] αシヌクレインの生理作用2013

    • Author(s)
      関山一成、高松芳樹、橋本款
    • Publisher
      医学のあゆみ
    • Related Report
      2013 Research-status Report
  • [Book] Ibuprofen: Clinical Pharmacology, Medical Uses and Adverse Effects.2013

    • Author(s)
      Sekiyama K, Fujita M, Sekigawa A, Takamatsu Y, Hashimoto M.
    • Publisher
      InTech
    • Related Report
      2013 Research-status Report
  • [Book] Emerging Drugs and Targets for Parkinson's Disease.2013

    • Author(s)
      Takenouchi T, Sekiyama K, Fujita M, Sugama S, Iwamaru Y, Kitani H, Hashimoto M.
    • Publisher
      Royal Society of Chemistry
    • Related Report
      2013 Research-status Report
  • [Remarks] 公益財団法人 東京都医学総合研究所 パーキンソン病研究室

    • URL

      http://www.igakuken.or.jp/parkinson/

    • Related Report
      2015 Annual Research Report

URL: 

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

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