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老年痴呆の分子機構

Research Project

Project/Area Number 04268101
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Research InstitutionKyushu University (1993)
Tokyo Medical and Dental University (1992)

Principal Investigator

立石 潤 (1993)  九州大学, 医学部, 教授 (70033305)

宮武 正 (1992)  東京医科歯科大学, 医学部, 教授 (50048998)

Co-Investigator(Kenkyū-buntansha) 高久 史麿 (高久 央麿)  国立病院医療センター, 院長 (40048955)
今堀 和友  三菱化成, 生命科学研究所, 所長 (40012174)
辻 省次  新潟大学, 脳研究所, 教授 (70150612)
井原 康夫  東京大学, 医学部, 教授 (60114386)
畠中 寛  大阪大学, 蛋白質研究所, 教授 (60208519)
立石 潤  九州大学, 医学部, 教授 (70033305)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥31,100,000 (Direct Cost: ¥31,100,000)
Fiscal Year 1993: ¥19,000,000 (Direct Cost: ¥19,000,000)
Fiscal Year 1992: ¥12,100,000 (Direct Cost: ¥12,100,000)
Keywordsアルツハイマー病 / アルツハイマー型老年痴呆 / アミロイド前駆体蛋白 / 家族性アルツハイマー病 / タウ蛋白 / 成長抑制因子 / 神経原線維変化 / リン酸化 / 神経成長因子
Research Abstract

本研究は、老年期に生じる痴呆性疾患の中から、とくに現在まだ病因の解明がなされていないアルツハイマー型老年痴呆(アルツハイマー病)を中心課題としてとりあげ、その発症機構を以下の3点の主要研究項目のもとに解明することを目的としている。すなわち、研究項目としては、〓脳老化と神経栄養因子 〓アルツハイマー病脳内蓄積物質の形成機序 〓アルツハイマー病の分子遺伝学的研究がある。〓においては、神経成長因子に代表される神経栄養因子の働き、とくに脳損傷や老化に伴う変動が調べられた。〓においてはアミロイド前駆体蛋白(APP)からAbetaアミロイが生じる機序と関連酵素、タウ蛋白のリン酸化と脱リン酸化酵素などを中心に調べ新しい知見を得た。さらにタウ蛋白遺伝子を除去したマウスが作られた意義は大きい。〓においては家族性アルツハイマー病を中心に染色体14,19,21番を調べ、またAPP遺伝子を除去する計画が進行中である。これらの各班の研究は密接な連携のもとに進行し、平成5年8月5日には合同ワークショップを開催し、翌6日には公募演題を中心に討論を行なった。さらに12月21日には全班員の研究成果の発表があり、22日には公開シンポジウム「アルツハイマー病の病因を探る」を開催した。この間に総括班会議、企画運営委員会、班長会議などを頻回に開催した。さらに11月17日から3日間、神奈川県大磯市で開催された老年痴呆をめぐる国際会議で班員の多くが発表し、ほぼ全員の参加があり、多くの成果が得られた。

Report

(2 results)
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Ohgami,T.: "A lack of novel APP677 expression in brain." J.Neurochem.61. 1553-1556 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohgami,T.: "Alzheimer's amyloid precursor protein mRNA without exon 15 is ubiquitously expressed except in the rat central nervous system." Mol.Brain Res.20. 240-244 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Enokido,Y.: "Apoptotic cell death occurs in hippocampal neurons cultured in high oxygen atmosphere." Neurosci.57. 965-972 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akaneya,Y.: "in vitro model of hypoxia:basic fibroblast growth factor can rescue cultured CNS neurons from oxygen-deprived cell death." J.Cereb.Blood Flow Metab.13. 1029-1032 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morishima-Kawashima,M.: "Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments." Neuron. 10. 1151-1160 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Watanabe,A.: "In vivo phosphorylation sites in fetal and abult rat tau." J.Biol.Chem.268. 25712-25717 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tanaka,H.: "Absence of linkage disequilibrium at amyloid precursor protein gene locus in Japanese familial Alzheimer's disease with 77Val→Ile mutation." Nippon Rinsho. 51. 3452-3456 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Mullan,M.: "Clinical comparison of Alzheimer's disease in pedigrees with the codon 717 Val→Ile mutation in the amyloid precursor protein gene." Neurobiol.14. 407-419 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takashima,A.: "Tau protein kinase I is essential for amyloid protein-induced neurotoxicity." Proc.Natl.Acad.Sci.USA. 90. 7789 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ishiguro,K.: "Glycogen synthase kinase 3beta is identical to tau protein kinase I generating several epitopes of paired helical filaments." FEBS Lett.325. 167-172 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 高久 史麿: "新しい医療の展開-癌、エイズ、痴呆、動脈硬化を中心に。" 日本医事新報. 3586. 3-13 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Furukawa,S.: "Opening of ATP-sensitive K^+ channels responsible for adenosine A_2receptormediated vasodepression does not involve a pertussis toxin-sensitive G protein." Eur.J.Pharmacol.236. 255-262 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] T.Nonomura and H.Hatanaka: "Neurotrophic effect of brain-derived neurotrophic factor on basal forebrain cholinegic newrons in culture from prstnatal rats." Neuroscience Research. 14. 226-233 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Kushima,C.Nishio,T.Noromura and H.Hatanaia: "Effects of nerve growth factor and basic fibrdlat growth factor on survival of cultured cho linergic neurons from abult rats." Brain Research. 598. 264-270 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Ohganmi,T.Kitamoto and J.Tateishi: "Alzheimers's amyloid precursor protein accumulates within axonal swellings in human brain lesions." Neurosci,Lett.136. 75-78 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Miyazono,T.Kitamoto,T.Iwaki and J.Tateishi: "Colocalization of prion protein and β protein in the same amyloid plaques in patients with Gerstmann-Straussler Syndrome." Acta Neuropathol.83. 333-339 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Tsuji,H.Kobayashi,Y.Uchida,Y.Ihara and T.Miyatake: "Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease." EMBOJ.11(13). 4843-4850 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Kaneko,H.Kobayashi,O.Onodera,T.Miyatake and S.Tsuji: "Genomic organization of a cDNA (QM) demonstrating an altered mRNA level in nontumorigenic Wilms' microcell hybrid cells and its location to Xq28." Hum.Mol.Genet.1(7). 529-533 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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