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Role of cyclin-dependent kinase 5 in Alzheimer's brain.

Research Project

Project/Area Number 09044317
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Neuroscience in general
Research InstitutionKagawa Medical University

Principal Investigator

TOKUDA Masaaki  Kagawa Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10163974)

Co-Investigator(Kenkyū-buntansha) SUGIMOTO Katsuyoshi  Kagawa Medical University, Faculty of Medicine, Research Associate, 医学部, 客員教員
MIYAMOTO Osamu  Kagawa Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00253287)
KOBAYASHI Ryoji  Kagawa Medical University, Faculty of Medicine, Professor, 医学部, 教授 (00020917)
YAMAGUCHI Fuminori  Kagawa Medical University, Faculty of Medicine, Research Associate, 医科部, 助手 (40271085)
ITANO Toshifumi  Kagawa Medical University, Faculty of Medicine, Professor, 医学部, 教授 (60145042)
HANS van de  カルガリ大学, 副医学部長
後藤 孝也  香川医科大学, 医学部, 助手 (80284355)
長畠 駿一郎  香川医科大学, 医学部, 教授 (10033375)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordscyclin-dependent kinase / p35 / phosphorylation / plasticity / Alzheimer's disease / neuronal degeneration / tau-protein / neurofilament / アルツハイマー脳 / Cdk5
Research Abstract

1. Expression levels and kinase activity of cychn-dependent kinase 5 (Cdk5) and its activator p35 were analyzed and compared using 8 Alzheimer's brains and 18 age-matched normal brains.
2. Western blot analysis using specific antibodies for two proteins elucidated that Cdk5 and p35 increased by 20% and 15%, respectively, in Alzheimer's brains as compare with those in control brains.
3. Cdk5/p35 activity in Alzheimer's brains was 20% higher than that in control brains. Especially, the activity in hippocampus in Alzheimer' s brains increased by 30%, however, that in forebrain did not increase significantly,
4. Immunohistochemical study elucidated that distribution of both Cdk5 and p35 was dominantly observed at the regions of paired helical tangles which is characteristic in Alzheimer's brains.
5. Southern blot analysis of Cdk5 and p35 showed no significant difference between Alzheimer's brains and control brains.
6. Several proteins were assayed for the stimulatory or inhibitory activity of Cdk5/p35 activity, and S100A and B showed no stimulation or inhibition. Calbrain which we recently cloned showed a significant stimulation on the kinase activity.
7. None of cAMP-dependent protein kinase, calcium/phospholipid-dependent protein kinase, calmodulin-dependent protein kinase 2 and casein kinase phosphorylated Cdk5/p35 and did not alter its activity.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] F.Yamaguchi: "Molecular cloning of 5-hydroxytryptamine (5-HT) type 1 receptor genes from the Japanese puffer fish Fugu rubripes" Gene. 191. 219-223 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tokuda: "Involvement of calmodulin-dependent protein kinase I and IV in long term potentiation" Brain Research. 755・1. 162-166 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Morita: "Fos induction in rat brain neurons following stimulation of the hepatoportal Na-sensitive mechanism" American Journal of Physiology. 272. R913-R923 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Hirooka: "A novel calcium/calmodulin-dependent protein kinase IV like protein in rat retina" Vision Research. 37. 2029-2033 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Gotoh: "Activation of R-Ras by Ras-guanine nucleotide-releasing factor" Journal of Biological Chemistry. 272(30). 18602-18607 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] X-H.Cai: "Changes in the expression of novel Cdk5 activator messenger RNA (p39^<nck5ai>mRNA) during rat brain development" Neuroscience Research. 28. 355-360 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Oyama: "Two distinct anti-allergic drugs, amlexanox and cromolyn, bind to the same kinds of calcium binding proteins, except calmodulin, in bovine lung extract" Biochemical and Biophysical Research Communications. 240. 341-347 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tokuda: "Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation" Molecular Neurobiology. 17・1-3. 137-156 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] F.M.Musa: "Expression of cyclin-dependent kinase 5 and associated cyclins in leydig and sertoli cells of the testis" Journal of Andorology. 19.6. 657-666 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Shishibori: "Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A 13 of the S100 protein family" Biochem.J.338. 583-589 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] F.Yamaguchi et al.: "Molecular cloning of 5-hydroxytryptamine(5-HT)type 1 receptor genes from the Japanese puffer fish Fugu rubripes." Gene. 191. 219-223 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tokuda et al.: "Involvement of calmodulin-dependent protein kinase I and IV in long term potentiation." Brain Research. 755(1). 162-166 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Morita et al.: "Fos induction in rat brain neurons following stimulation of the hepatoportal Na-sensitive mechanism." American Journal of Physiology. 272. R913-R923 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Hirooka et al.: "A novel calcium/calmodulin-dependent protein kinase IV like protein in rat retina." Vision Research. 37. 2029-2033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Gotoh et al.: "Activation of R-Ras by Ras-guanine nucleotide-releasing factor." Journal of Biological Chemistry. 272(30). 18602-18607 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] X-H.Cai et al.: "Cahnges in the expression of novel Cdk5 activator messenger RNA (p39^<nck5ai> mRNA) during rat brain development." Neuroscience Research. 28. 355-360 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Oyama et al.: "Two distinct anti-allergic drugs, amlexanox and cromolyn, bind to the same kinds of calcium binding proteins, except calmodulin, in bovine lung extract." Biochemical and Biophysical Research Communications. 240. 341-347 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Tokuda et al.: "Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation." Molecular Neurobiology. 17(1-3). 137-156 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] F.M.Musa et al.: "Expression of cyclin-dependent kinase 5 and asociated cyclins in leydig and sertoli cells of the testis." Journal of Andorology. 19(6). 657-666 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Shishibori et al.: "Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family." Biochem.J.338. 583-589 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Oyama: "Two distinct anti-allergic drugs,amlexanox and cromolyn,bind to the same kinds of calcium binding proteins,except calmodulin,in bovine lung extract" Biochem.Biophys.Res.Commun.240. 341-347 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Tokuda: "Regulation of neuronal plasticity in the central nervous system by phosphorylation and dephosphorylation" Molecular Neurobiology. 17・1-3. 137-156 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.M.Musa: "Expression of cyclin-dependent kinase 5 and associated cyclins in leydig and sertoli cells of the testis" Journal of Andorology. 19・6. 657-666 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Shishibori: "Three distinct anti-allergic drugs amlexanox,cromolyn and tranilast,bind to S100A12 and S100A13 of the S100 protein family" Biochem J.338. 583-589 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fuminori Yamaguchi: "Molecular cloning of 5-hydroxytryptamine (5-HT) type 1 receptor genes from the Japanese puffer fish Fugu rubripes." Gene. 191. :219-223 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masaaki Tokuda: "Involnement of calmodulin-dependent protein kinases I and IV in long term potentiation." Brain Research. 755・1. 162-166 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hironobu Morita: "Fos induction in rat brain neurons following stimulation of the hepatoportal Na-sensitive mechanism." American Journal of Physiology. 272. R913-R923 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kazuyuki Hirooka: "A novel calcium/calmodulin-dependent protein kinase IV like protein in rat retina." Vision Research. 37. 2029-2033 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takaya Gotoh: "Activation of R-Ras by Ras-guanine nucleotide-releasing factor." Journal of Biological Chemistry. 272・30. 18602-18607 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Xiao-Hui Cai: "Changes in the expression of novel Cdk5 activator messenger RNA (p39nck5ai mRNA) during rat brain development." Neuroscience Research. 28. 355-360 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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