• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Neuroprotective mechanism of carnosine against zinc-induced neurotoxicity: a possible drug for vascular dementia

Research Project

Project/Area Number 26460177
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionMusashino University

Principal Investigator

Kawahara Masahiro  武蔵野大学, 薬学研究所, 教授 (40224828)

Co-Investigator(Kenkyū-buntansha) 水野 大  山形大学, 医学部, 准教授 (70380061)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords神経毒性 / 亜鉛 / 銅 / カルシウム / 小胞体ストレス / アルツハイマー病 / プリオン病 / 老年性認知症 / 神経細胞死 / カルシウムホメオスタシス / ARDS / 肺疾患 / 抗酸化 / 運動能力 / アポトーシス / HPLC / carnosine / ER stress / Zn / amyloid / anserine / dementia / Alzheimer
Outline of Final Research Achievements

Carnosine (β-alanyl histidine) is a small dipeptide abundantly present in the muscloes and brains. Carnosine has numerous beneficial characteristics, including the maintenance of the acid-base balance, antioxidant, metal chelating, anti-crosslinking, and anti-glycation activities. We investigated the neuroprotective effects of carnosine and the related compounds, and found that carnosine attenuated zinc-induced neurodegeneration, which plays central roles in the pathogenesis of vascular dementia. Furthermore, carnosine and its analogue anserine inhibited zinc-induced endoplasmic reticulum (ER)-stress, and attenuated the neurotoxicity induced by ER-stress inducers such as thapsigargin. We developed a convenient method to quantify the amount of carnosine using HPLC equipped with the carbon column, and investigated the amount of carnosine and anserine in various foods or in muscles of Thoroughbred horses. Our results are useful in the development of drugs for vascular dementia.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (39 results)

All 2017 2016 2015 2014

All Journal Article (15 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 5 results,  Acknowledgement Compliant: 7 results) Presentation (19 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (5 results)

  • [Journal Article] Cross talk between neurometals and amyloidogenic proteins at the synapse and the pathogenesis of neurodegenerative diseases2017

    • Author(s)
      Kawahara M, Kato-Negishi M, Tanaka K
    • Journal Title

      Metallomics

      Volume: 5 Issue: 6 Pages: 619-633

    • DOI

      10.1039/c7mt00046d

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Preventive Effects of Carnosine on Lipopolysaccharide-induced Lung Injury.2017

    • Author(s)
      Tanaka K, Sugizaki T, Kanda Y, Tamura F, Niino T, Kawahara M.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 42813-42813

    • DOI

      10.1038/srep42813

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Evaluation of Lecithinized Superoxide Dismutase for the Prevention of Acute Respiratory Distress Syndrome in Animal Models2017

    • Author(s)
      Tanaka KI, Tamura F, Sugizaki T, Kawahara M, Kuba K, Imai Y, Mizushima T
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 56(2) Issue: 2 Pages: 179-190

    • DOI

      10.1165/rcmb.2016-0158oc

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 神経疾患と微量元素2017

    • Author(s)
      川原正博
    • Journal Title

      臨床検査

      Volume: 61 Pages: 174-178

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice2017

    • Author(s)
      Tanaka K, Niino T, Ishihara T, Sugizaki T, Takafuji A, Takayama T, Kanda Y, Tamura F, Kurotsu S, Kawahara M, Mizushima T
    • Journal Title

      Scientific Reports

      Volume: 7

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 微量元素の生体機能と疾患-アルミニウムと神経疾患2016

    • Author(s)
      川原正博
    • Journal Title

      日本臨床

      Volume: 74 Pages: 1176-1185

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Journal Article] Protective activity of carnosine and anserine against zinc-induced neurotoxicity: a possible treatment for vascular dementia.2015

    • Author(s)
      Mizuno D et al
    • Journal Title

      Metallomics

      Volume: 印刷中 Issue: 8 Pages: 1-7

    • DOI

      10.1039/c5mt00049a

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Carnosine concentration in the muscle of thoroughbred horses and its implications in exercise performance2015

    • Author(s)
      M.Mori, D.Mizuno, K.Konoha-Mizuno, Y.Sadakane, M.Kawahara
    • Journal Title

      Trace Nutrients Research

      Volume: 32 Pages: 49-53

    • NAID

      40020919697

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Quantitative analysis of carnosine and anserine in foods by performing high performance liquid chromatography2015

    • Author(s)
      Mori, D. Mizuno, K. Konoha-Mizuno, Y. Sadakane, M. Kawahara
    • Journal Title

      Biomedical Research on Trace Elements

      Volume: 26 Pages: 49-53

    • NAID

      130005113917

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Quantification of horse plasma proteins altered by xylazine using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry2015

    • Author(s)
      4.M.Mori, T. Ichibangase, S. Yamashita, I.Kijima-Suda, M. Kawahara, K.Imai
    • Journal Title

      J. Equine Sci.

      Volume: 26 Pages: 141-146

    • NAID

      130005124609

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 微量元素と神経疾患:シナプス間隙における疾患関連タンパクと金属との相互作用2015

    • Author(s)
      川原正博、水野大
    • Journal Title

      Biomed Trace Elem Res

      Volume: 26 Pages: 10-22

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of trace elements in the pathogenesis of prion diseases2014

    • Author(s)
      Mizuno D, Koyama H, Ohkawara S, Sadakane Y, Kawahara M
    • Journal Title

      Curr Pharam Biotech

      Volume: 15 Pages: 1049-57

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Carnosine: A Possible Drug for Vascular Dementia.2014

    • Author(s)
      Mizuno D et al.
    • Journal Title

      J Vasc Med Surg

      Volume: 2 Issue: 03 Pages: 146-146

    • DOI

      10.4172/2329-6925.1000146

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ニューロメタルとアミロイド形成タンパク質のクロストーク2014

    • Author(s)
      川原正博、水野大
    • Journal Title

      日本衛生学雑誌

      Volume: 69 Pages: 155-165

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] 神経疾患と亜鉛2014

    • Author(s)
      川原正博、定金豊、水野大
    • Journal Title

      亜鉛栄養治療

      Volume: 5 Pages: 4-15

    • NAID

      40020474970

    • Related Report
      2014 Research-status Report
  • [Presentation] 食品中カルノシンのcarbon カラムHPLC による定量分析2017

    • Author(s)
      田中 健一郎, 森 美和子, 水野 大, 定金 豊, 川原 正博
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2017-03-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] LPS急性肺傷害に対する抗酸化ペプチド・カルノシンの予防効果の検討2017

    • Author(s)
      神田侑季、川原正博、田中健一郎
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] サラブレッド筋肉中のカルノシン濃度:筋肉種による差異と運動能力との関連2016

    • Author(s)
      森美和子、川原正博
    • Organizer
      第58回競争馬に関する調査研究発表会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2016-11-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Metal-metal interactions in zinc-induced neurotoxicity: the possible involvements in the pathogenesis of vascular dementia2016

    • Author(s)
      Kawahara M, Mizuno D, Tanaka K.
    • Organizer
      Neuroscience 2016
    • Place of Presentation
      SanDiegoConvention center (San Diego, U.S.A.)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 食品中カルノシンの定量分析および肺障害に対する効果2016

    • Author(s)
      田中健一郎、川原正博
    • Organizer
      新アミノ酸分析研究会第6回学術講演会
    • Place of Presentation
      武田先端知センター(東京)
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 亜鉛による神経細胞死における金属間相互作用2016

    • Author(s)
      川原正博、田中健一郎
    • Organizer
      第27回日本微量元素学会学術集会
    • Place of Presentation
      京都大学(京都)
    • Year and Date
      2016-07-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] 食品中カルノシンおよびアンセリンのHPLCによる定量分析2016

    • Author(s)
      桒原奈緒美、森 美和子、水野 大、田中健一郎、川原正博
    • Organizer
      第33回日本微量栄養素学会学術集会
    • Place of Presentation
      京都リサーチパーク(京都)
    • Year and Date
      2016-06-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 筋肉中カルノシンおよびアンセリンの順相HPLCによる定量分析2015

    • Author(s)
      森 美和子、水野 大、水野-木葉敬子、定金 豊、川原正博
    • Organizer
      新アミノ酸分析研究会
    • Place of Presentation
      東京大学(東京)
    • Year and Date
      2015-12-07
    • Related Report
      2015 Research-status Report
  • [Presentation] カルノシンおよびアンセリンのHPLCによる定量分析およびその神経保護作用機構の解析2015

    • Author(s)
      森美和子、水野大、定金豊、川原正博
    • Organizer
      第28回バイオメディカル分析化学シンポジウム
    • Place of Presentation
      長崎大学(長崎)
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
  • [Presentation] カルノシンによる神経細胞保護メカニズムの解析2015

    • Author(s)
      川原正博、水野大
    • Organizer
      日本微量元素学会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2015-07-04
    • Related Report
      2015 Research-status Report
  • [Presentation] Molecular Mechanism of Neuroprotective activity by Carnosine and Anserine2015

    • Author(s)
      Mizuno D, Mori M, Asakawa N, Murohisa K, Yamamoto R, and Kawahara M
    • Organizer
      第25回金属の関与する生体関連反応シンポジウム(SRM2015)
    • Place of Presentation
      長崎大学(長崎)
    • Year and Date
      2015-05-30
    • Related Report
      2015 Research-status Report
  • [Presentation] カルノシンの神経保護作用及び筋肉中含量の解析2015

    • Author(s)
      森美和子、木葉―水野敬子、水野大、定金豊、川原正博
    • Organizer
      第32回日本微量栄養素学会
    • Place of Presentation
      京都
    • Year and Date
      2015-05-30
    • Related Report
      2015 Research-status Report
  • [Presentation] カルノシン、アンセリン類の順相HPLCによる分離分析およびその神経細胞死抑制機構の解析2014

    • Author(s)
      水野 大、菅亜由美、小林清美、小山 裕也、定金 豊、川原正博
    • Organizer
      第4回新アミノ酸分析研究会
    • Place of Presentation
      東京大学(東京都)
    • Year and Date
      2014-11-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Involvement of endoplasmic reticulum stress and calcium dyshomeostasis in zinc-induced neurotoxicity2014

    • Author(s)
      Dai MIZUNO and Masahiro KAWAHARA
    • Organizer
      Neuroscience2014(Society for Neuroscience Meeting)
    • Place of Presentation
      Convention Center(Washington DC, U.S.A.)
    • Year and Date
      2014-11-15 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳内のヤヌス~神経疾患発症における亜鉛の役割~2014

    • Author(s)
      川原正博
    • Organizer
      第9回近畿亜鉛栄養治療研究会
    • Place of Presentation
      シノテスト(大阪)
    • Year and Date
      2014-08-02
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 亜鉛による神経細胞死メカニズムの検討2014

    • Author(s)
      川原 正博、水野 大
    • Organizer
      日本微量元素学会第25回年会シンポジウム「ジンクシグナリングの最前線」
    • Place of Presentation
      岡山大学(岡山市)
    • Year and Date
      2014-07-03 – 2014-07-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 神経疾患と微量元素2014

    • Author(s)
      川原 正博、水野 大
    • Organizer
      日本微量元素学会第25回年会シンポジウム「疾患と微量元素」
    • Place of Presentation
      岡山大学(岡山市)
    • Year and Date
      2014-07-03 – 2014-07-04
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 金属が脳内アミロイド蛋白のコンフォメーション変化及び神経毒性に及ぼす影響2014

    • Author(s)
      川原正博、水野大
    • Organizer
      第41回日本毒性学会学術年会シンポジウム
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2014-07-02
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 亜鉛神経細胞死におけるカルノシンの役割2014

    • Author(s)
      水野大、菅亜由美、川原正博
    • Organizer
      第24回金属の関与する生体関連反応シンポジウム(SRM2014)
    • Place of Presentation
      京都薬科大学(京都)
    • Year and Date
      2014-06-17 – 2014-06-18
    • Related Report
      2014 Research-status Report
  • [Book] Metallomics-Recent Analytical Techniques and Applications-, (eds Ogra,Y and Hirata, T)2017

    • Author(s)
      Mizuno D and Kawahara M
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Disruption of metal homeostasis and the pathogenesis of prion diseases Prion2016

    • Author(s)
      Kawahara M, Tanaka K, and Mizuno D
    • Publisher
      InTech
    • Related Report
      2016 Annual Research Report
  • [Book] Carnosine: Physiological Effects and Research Insights2016

    • Author(s)
      Kawahara M, Tanaka K and Mizuno D
    • Publisher
      Nova Science Publishers
    • Related Report
      2016 Annual Research Report
  • [Book] Aluminum Neurotoxicity: From Subtle Molecular Lesions to Neurological Diseases2016

    • Author(s)
      Kawahara M
    • Publisher
      Nova publication
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Book] Oligomerization (ed by Claire Lesieur, ISBN 980-953-307-1130-3)2014

    • Author(s)
      Mizuno D and Kawahara M
    • Total Pages
      450
    • Publisher
      InTech
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi