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Studies on mechanisms of neurodegeneration by Abeta-amyloid

Research Project

Project/Area Number 09044288
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Neurochemistry/Neuropharmacology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

UEDA Kunihiro  KYOTO UNIVESITY,INSTITUTE FOR CHEMICAL RESEARCH,PROFESSOR, 化学研究所, 教授 (00027070)

Co-Investigator(Kenkyū-buntansha) SAMOCHOCKI M  ポーランド科学アカデミー, 医学研究センター, 助手
STROSZNAJDER ジョアンナ  ポーランド科学アカデミー, 医学研究センター, 教授
TANAKA Seigo  KYOTO UNIVESITY,INSTITUTE FOR CHEMICAL RESEARCH,ASSOCIATE PROFESSOR, 化学研究所, 助教授 (70263150)
MAREK Samochocki  POLISH ACADEMY OF SCIENCES,MEDICAL RESEARCH CENTRE,ASSISTANT PROFESSOR
JOANNA Strosznajder  POLISH ACADEMY OF SCIENCES,MEDICAL RESEARCH CENTRE,PROFESSOR
安達 善文  京都大学, 化学研究所, 助手 (50201893)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsAlzheimer's disease / Abeta amyloid / apoptosis / NAC / poly (ADP-ribose) synthetase / nitric oxide (NO) / NO synthetase (NOS) / NMDA receptor / PC12細胞 / NO(一酸化窒素) / NOS(NO合成酵素) / α-シヌクレイン / ポリ(ADP-リボース) / PARS
Research Abstract

1. Analysis of Mechanism of Neuronal Death Caused by Abeta Amyloid (the Japanese Group)
(1)Induction of neuronal death by Abeta amyloid
The 25-35 fragment of Abeta peptide (Abeta25-35) proved to be toxic in differentiated PC 12 cells at a concentration of 100 nM.Part of the cells showed chromatin aggregation and DNAfragmentation, suggesting that neuronal death in the brain of Alzheimer's disease (AD) is caused, at least partly, by apoptosis.
(2)Promotion of Abeta amyloid formation by NAC
NAC (Non-Abeta component of AD amyloid) was shown to be as amyloidogenic and neurotoxic as Abeta25-35 peptide and also promotive of Abeta aggregation. This result suggests that the coexistence of Abeta and ANC peptides facilitates amyloid formation and enhances neuronal injury.
(3)Implication of poly(ADP-ribose) synthetase (PARS) in neuronal death Abeta amyloid induced initial activation of PARS, followed by rapid inactivation) This change suggests a relationship between the activity , change and the cleavage of PARS during neuronal injury by Abeta amyloid.
2. Studies on Role of Nitric Oxide (NO) in Neuronal Death (the Polish Group)
The mechanism of neurotoxicity of Abeta amyloid was analyzed with
reference to intracellular signaling, particularly the NO cascade. The activity of NMDA recepter-mediated and Ca^<2+>/calmodulin-dependent NOS (nitric oxide synthase) was lower in the hippocampus and cerebellum in aged rat. Afbeta25-35 had no effect on the NOS activity in the basal condition, but reduced NMDA-responsive NOS activation. These results suggest the possibility that Abeta amyloid interferes with the intracellular signaling of NO cascade induced by NMDA.

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] Tokime, T., et al.: "Enhanced poly (ADP-ribosyl) ation after focal isochemia in rat brain" J.Cerebral Blood Flow Metab.18. 991-997 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, S., et al.: "Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimers disease" Neurology. 50・6. 1556-1562 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ariumi, Y., et al.: "In vivo phosphorylation of poly (ADP-ribose) polymerase is independent of its activation" FEBS Lett.436. 288-292 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, S., et al.: "Inferior temporal lobe atrophy and APOE genotypes in Alzheimer's disease. X-ray computes tomography, magnetic resonance imaging and Xe-133 SPECT studies" Dement.Geriatr.Cogn. Disord.9・1. 90-98 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Banasik, M., et al.: "Dual inhibitory effects of dimethyl sulfoxide on poly (ADP-ribose) synthetase" J.Enz.Inhib.14・3. 239-250 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ariumi, Y., et al.: "Suppression of poly (ADP-ribose) polymerase activity by DNA-dependent protein kinase" Oncogene. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 上田國寛: "メディコピア 第38巻(遺伝子医療-いまとこれから)" 第18回メディコピア教育講演シンポジウム, 158 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 上田國寛: "岩波講座「現代医学の基礎」第1巻" 岩波書店, 267 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokime, T., et al.: "Enhanced poly (ADP-ribosyl) ation after focal isochemia in rat brain" J.Cerebral Blood Flow Metab.18. 991-997 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, S., et al.: "Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimer's disease" Neurology.50・6. 1556-1562 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ariumi, Y., et al.: "In vivo phosphorylation of poly (ADP-ribose) polymerase is independent of its activation" FEBS Lett.436. 288-292 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanaka, S., et al.: "Inferior temporal lobe atrophy and APOE genotypes in Alzheimer's disease.X-ray computes tomography, magnetic resonance imaging and Xe-133 SPECT studies" Dement.Geriatr.Cogn.Disord.9・1. 90-98 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Banasik, M., et al.: "Dual inhibitory effects of dimethyl sulfoxide on poly (ADP-ribose) synthetase" J.Enz.Inhib.14・3. 239-250 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ariumi, Y., et al.: "Suppression of poly (ADP-ribose) polymerase activity by DNA-dependent protein kinase" Oncogene.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueda, K.: Medicopia vol.38 Gene Therapy : Now and Future.The 18th Medicopia Educational Lecture Symposium (Tokyo, January 11,1998), 158 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueda, K.: Bases for Moderm Medicine, vol.1. Iwanami, Tokyo., 267 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tokime,T.,et al.: "Enhanced poly(ADP-ribosyl)ation after focal isochemia in rat brain" J.Cerebral Blood Flow Metab.18. 991-997 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,S.,et al.: "Association of CYP2D microsatellite polymorphism with Lewy body variant of Alzheimers disease" Neurology. 50・6. 1556-1562 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ariumi,Y.,et al.: "In vivo phosphorylation of poly(ADP-ribose)polymerase is independent of its activation" FEBS Lett.436. 288-292 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Banasik,M.,et al.: "Dual inhibitory effects of dimethyl sulfoxide on poly(ADP-ribose)synthetase" J.Enz.Inhib.14・3. 239-250 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ariumi,Y.,et al.: "Suppression of poly(ADP-ribose)polymerase activity by DNA-dependent protein kinase" Oncogene. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田國寛: "ナイアシンとアポトーシス" ビタミン. 72・5,6. 218-220 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田國寛: "メディコピア第38巻(遺伝子医療-いまとこれから)" 第18回メディコピア教育講演シンポジウム, 158 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田國寛: "岩波講座「現代医学の基礎」第1巻" 岩波書店, 267 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Li, S., et al.: "Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression" J.Neutopathol.Exp.Neurol.56. 901-911 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka, S., et al.: "Inferior temporal lobe atrophy and APOE genotypes in Alzheimer's disease.X-ray computed tomography,magnetic resonance imaging and Xe-133 SPECT studies" Dement.Geriatr.Cogn.Disord.9・1. 90-98 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanaka, S., et al.: "Association of microsattellite polymorphism in the CYP2D locus with Lewy body variant of Alzheimer's disease" Neurology. 20(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 田中 静吾: "アルツハイマー病の遺伝子診断" 最新医学. 52・増. 2160-2169 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 田中 静吾・上田 國寛: "アルツハイマー病の原因遺伝子とその発症のメカニズム" 遺伝子医学. 1・1. 62-71 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 田中 静吾: "アルツハイマー病とパーキンソン病の発症に共通して関与するNACP/α-シヌクレイン" 化学と生物. 36・(4). 786-787 (1998)

    • Related Report
      1997 Annual Research Report

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

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