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Molecular mechanism of neuronal cell death in Alzheimer's disease

Research Project

Project/Area Number 08680837
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionCancer, Research Institute, Kanazawa University

Principal Investigator

YOSHIOKA Katsuji  Cancer Research Institute, Kanazawa University, Associate Professor, がん研究所, 助教授 (60200937)

Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsAlzheiwer's disease / signal transduction
Research Abstract

The selective neuronal degeneration in Alzheimer's disease (AD) has not been extensively studied, mainly due to few specific histological or molecular markers for neuronal subpopulations. Moreover, the intracellular signaling pathway involved in the neuronal degeneration remains to be analyzed. JNK3, a member of mitogen-activated protein kinase, expresses in a subset of neurons of the human nervous system. The distribution of these neurons closely matches that of AD targeted neurons. As a first step to clarify the JNK3 cascade, we have carried out yeast two-hybrid system to isolate cDNA clones of JNK3-binding proteins. One of the JNK3-binding proteins (termed BP#2) expresses exclusively in brain as JNK3. BP#2 can be a sustrate of JNK3, and the phosphorylated BP#2 no longer binds with the activated JNK3. Furthermore, we have found that BP#2 associates with not only JNK3 but also SEK1, an activator of JNK3. These results suggest that BP#2 works as a scaffold protein in the JNK3 cascade. The JNK3/BP#2 complex would dissociate through the phosphorylation of BP#2 done by JNK3.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] 善岡 克次: "アルツハイマー病における神経細胞死機構" 日本老年医学会雑誌. 35. (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Onishi et al.: "Activation of c-Jun N-terminal kinase during ischemia and reperfusion in mouse liver" FEBS Letters. 420. 201-204 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Mizukami et al.: "A novel mechanism of JNK1 activation" J.Biol.Chem.272. 16657-16662 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Yoshioka: "Molecular mechanism of neuronal cell death in Alzheimer's disease" Jpn.J.Geriat. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Onishi et al.: "Activation of c-Jun N-terminal kinase during ischemia and reperfusion in mouse liver" FEBS Lett.420. 201-204 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Mizukami et al.: "A novel mechanism of JNK1 activation" J.Biol.Chem.272. 16657-16662 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 善岡克治: "アルツハイマー病における神経細胞死機構" 日本老年医学会雑誌. 35. (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] I.Onishi et al.: "Activation of c-Jun N-terminal kinase during ischemia and reperfusion in mouse liver" FEBS Letters. 420. 201-204 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Mizukami et al.: "A novel mechanism of JNK1 activation" J.Biol.Chem.272. 16657-16662 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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