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2005 Fiscal Year Final Research Report Summary

Molecular mechanisms of cell death mediated by apolipoprotein E receptor family

Research Project

Project/Area Number 16601003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 細胞死(アポトーシス)
Research InstitutionEhime University

Principal Investigator

MITSUDA Moriaki  Ehime University, School of Medicine, Professor, 医学部, 教授 (10314329)

Co-Investigator(Kenkyū-buntansha) SUZUKI Yoji  Ehime University, School of Medicine, Lecturer, 医学部, 講師 (20226567)
AOTO Mamoru  Ehime University, School of Medicine, Lecturer, 医学部, 講師 (50372727)
Project Period (FY) 2004 – 2005
KeywordsApolipoprotein E receptor / Reelin / apoptosis
Research Abstract

The purpose of the research :
In former research, the claimants have reported that the apolipoprotein E(ApoE) which is secreted from the astrocytes and the microglias inhibit neuronal cell death through the ApoE receptors which exist in the neuronal cell surface. In the pathway, GSK-3β, which phosphorylates Tau protein, participated. Therefore, in this research, we analyze the difference of the apoptosis suppressing-function and in the intracellular signal transduction pathway by the difference of the ApoE receptor ligand. As the another ApoE receptor ligand, we deal with Reelin, this time.
The result :
Reelin protected P19 embryonal cells from apoptosis during retinoic-acid induced neuronal differentiation. This increased survival is associated with reelin activation of the phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway. When PI3K was inhibited with LY294002, reelin failed to protect against this retinoic-acid induced apoptosis. The protective effect of reelin includes activating the Src-family kinases/PI3K/Akt pathway which then led to selective phosphorylation of BAD at serine-136, while the phosphorylation-incompetent mutation of BAD (S136A) suppressed this protection.
The conclusion :
These studies define a novel pathway where reelin binds apoE receptors, significantly activates the PI3K/Akt pathway causing phosphorylation of BAD which helps to protect cells from apoptosing thus serving an important role in promoting the survival of maturing neurons in the brain.

  • Research Products

    (8 results)

All 2006 2005

All Journal Article (7 results) Book (1 results)

  • [Journal Article] A novel alternative splice variant of nicastrin and its implication in Alzheimer disease.2006

    • Author(s)
      Mitsuda N, et al..
    • Journal Title

      Life Sciences 78

      Pages: 2444-2448

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rbl, that upregulates Bcl-xL expression.2006

    • Author(s)
      Zhang B, et al.
    • Journal Title

      J Cereb Blood Flow Metab. 26

      Pages: 708-721

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A novel alternative splice variant of nicastrin and its implication in Alzheimer disease.2006

    • Author(s)
      Mitsuda N, et al.
    • Journal Title

      Life Sciences 78

      Pages: 2444-2448

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb1, that upregulates Bcl-xL expression.2006

    • Author(s)
      Zhang B, et al.
    • Journal Title

      J Cereb Blood Flow Metab. 26

      Pages: 708-721

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Dementia2006

    • Author(s)
      Ogihara T, et al.
    • Journal Title

      Geriatric disease and Dementia - the secret for longevity (in Japanese) 5

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Suppression of Stat3 promotes neurogenesis in cultured neural stem cells.2005

    • Author(s)
      Gu F, et al.
    • Journal Title

      J Neurosci Res. 81・2

      Pages: 163-171

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Suppression of Stat3 promotes neurogenesis in cultured neural stem cells.2005

    • Author(s)
      Gu F, et al.
    • Journal Title

      J Neurosci Res. 81

      Pages: 163-171

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 老年病・認知症 〜長寿の秘訣〜2006

    • Author(s)
      荻原 俊男(監修)(分担)
    • Total Pages
      5
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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