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2002 Fiscal Year Final Research Report Summary

Involvement of endoplasmic stress responses in Alzheimer disease

Research Project

Project/Area Number 13671002
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionOsaka University

Principal Investigator

KUDO Takashi  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10273632)

Co-Investigator(Kenkyū-buntansha) KATAYAMA Taiichi  Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80333459)
TANAKA Toshihisa  Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (10294068)
TAKEDA Masatoshi  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00179649)
Project Period (FY) 2001 – 2002
KeywordsAlzheimer disease / β-amyloid / endoplasmic retieulum / apoptosis / caspase
Research Abstract

Elevated levels of β-amyloid (Aβ) are present in the brains of individuals with either the sporadic or familial from of Alzheimer disease (AD), and the deposition of Aβ within the senile plaques that are a hallmark of AD is thought to be a primary cause of the cognitive dysfunction that occurs in AD. Recent evidence suggests that Aβ induces neuronal apoptosis in the brain and in primary neuronal cultures. It is also reported that responses for endoplasmic reticulum (ER) stress are involved in some neurodegenerative disorder including AD. In this study, we characterized a mechanism by which Aβ induces neuronal death. We found that in neurons exposed to A β, ER stress responses are activated, namely a phosphorylation of eIF2α and an induction, of GRP 78. It was also shown that the stress responses in ER by Aβ induces an activation of caspase 12 in mice or caspase 4 in human. Knock-down studies with dsRNA for caspase 12 or caspase 4 showed that apoptosis in neurons exposed to Aβ is mainly caused by the caspase related to ER. These findings raise the possibility that the ER stress pathway may contribute to Aβ -dependent death in AD patients.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Takayuki Manabe et al.: "The cytosolic inclusion bodies that consist of splice variants that lack exon 5 of the presenilin-2 gene differ obviously from Hirano bodies observed in the brain from sporadic cases of Alzheimer's disease patients"Neurosci. Lett.. 328. 198-200 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yuka Yasuda et al.: "Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin 1 mutations"Biochem Biophys Res Commun.. 296. 313-318 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masayasu Okochi et al.: "Presenilins mediate a dual intramembranous gamma-secretase cleavage of Notch-1"EMBO J. 21(20). 5408-5416 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kudo T et al.: "The unfolded protein response is involved in the pathology of Alzheimer's disease"Ann N Y Acad Sci. 977. 349-355 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 工藤 喬: "ERストレス"Clinical Neuroscience. vol.20. 647-649 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 工藤 喬: "小胞体ストレスと神経細胞死"Bio Clinica. vol.17. 792-796 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takashi Kudo et al.: "Mapping the Progress of Alzheimer's and Parkinson's Disease"Abraham Fisher. 565 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naoya Sato et al: "Increased production of β-amyloid and vulnerability to endoplasmic reticulum stress by as aberrant spliced form of presenilin 2"J Biol Chem.. 276(46). 43446-43454 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taiichi Katayama et al: "Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin 1 mutations"Biochim Biophys Acta. 1536(2-3). 85-96 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazunori Imaizumi et al: "The unfolded protein response and Alzheimer's disease"Neurosci. Lett.. 328. 198-200 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takayuki Manabe et al: "The cytosolic inclusion bodies that consist of splice variants that lack exon. 5 of the presenilin-2 gene differ obviously from Hirano bodies observed in the brain from sporadic cases of Alzheimer's disease patient"Biochem Biophys Res Common.. 296. 313-318 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yuka Yasuda et al: "FAD-linked presenilin-1 mutants impede translation regulation under ER stress"Ann N Y Acad Sci 2002 Nov. 977. 349-355 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takashi Kudo et al: "The unfolded protein response is involved in the pathology of Alzheimer's disease"J. Biol. Chem.. 276(3). 2108-2114 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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