1991 Fiscal Year Annual Research Report

脳の老化機構に関する分子細胞生物学的研究

Research Project

Project/Area Number	03224101
Research Institution	Tokyo Medical and Dental University
Principal Investigator	宮武正東京医科歯科大学, 医学部・神経内科, 教授 (50048998)
Co-Investigator(Kenkyū-buntansha)	今堀和友三菱化成, 生命科学研究所, 所長 (40012174) 榊佳之東京大学, 医科学研究所, 教授 (10112327) 三木直正大阪大学, 医学部, 教授 (40094445) 高木宏大阪市立大学, 医学部, 教授 (30163174) 立石潤九州大学, 医学部, 教授 (70033305)
Keywords	アルツハイマ-病 / 老年痴呆 / アミロイド前駆体蛋白 / βー蛋白 / 成長抑制因子
Research Abstract	人口の老齢化に伴う痴呆性老人の増加は、先進諸国の中でも我が国において大きな社会問題となっている。本研究は、老年期痴呆の二大原因(アルツハイマ-病と脳血管性痴呆)のうち、とくにアルツハイマ-病をとり上げ、原因求明、病態解明さらにはそれらの成果に基づき、治療法の開発の道を採る方向で進んで来た。具体的には、(1)アルツハイマ-病の脳に沈着する異常物質の生化学的解析とその処理機構、(2)アルツハイマ-病における伝達機構障害、(3)アルツハイマ-病における神経細胞死、(4)アルツハイマ-病に関連した遺伝子異常の解を、主要研究課題として、組織学、生化学、細胞生物学、分子遺伝学などの手法を駆使して研究を進めて来た。本研究班は、以上の研究を進めるにあたり、班の組組化、分担研究班間の連絡、情報交換を行なうとともに、班会議、公開シンポジウムを開催し、現在は研究成果のとりまとめを行なっている。本研究班による本年度の成果としては、アミロイド前駆体からβ蛋白が生じる段階で関与するプロテア-ゼ(シクレタ-ゼ)が明らかにされた。またアルツハイマ-病脳でダウンレギュレ-ションをうけていると考えられる成長抑制因子(GIF)の分子レベルでの研究が進み、活性部位が決定された。さらには、アミロイド前駆体蛋白遺伝子に点突然変異を有する家族性アルツハイマ-病の存在が、我が国においても確認され、欧米諸国に比較して、この点突然変異を有する割合が我が国において、極めて高いことが明らかになった。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Shin RW: "Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues." Lab.Invest.64. 693-702 (1991)
[Publications] Mori M: "Jc virus detection by in situ hybridization in brain tissue from elderly patient." Ann.Neurol.29. 428-432 (1991)
[Publications] Kuwabara T: "Study on the erythrocytes from myotonic dystrophy with multinuclear NMR." Muscle Nerve. 14. 57-63 (1991)
[Publications] S.Inagaki,H.Takagi,K.Suzuki,F.Akai and N.Taniguchi: "Intense immunoreactivity for Mn-superoxide dismutase(Mn-SOD) in cholinergic and non-cholinergic neurons in the rat basal forebrain." Brain Research. 541. 354-357 (1991)
[Publications] R.Tamiya,M.Hanada,S.Inagaki and H.Takagi: "Synaptic relation between neuropeptide Y axons and cholinergic neurons in the rat diagonal band of Broca." Neuroscience Letters. 122. 64-66 (1991)
[Publications] T.Araki and M.Tohyama: "Regionーspecific expression of GABA_A receptor α3 and α4 subunits mRNAs in the rat brain." Molecular Brain Research. 12. 293-314 (1992)
[Publications] J.H.Zhang,M.Sato and M.Tohyama: "Regionーspecific expression of the mRNAs encoding β subunits (β1,β2 and β3) of GABA_A receptor in the rat brain." The Journal of Comparative Neurology. 303. 637-657 (1991)
[Publications] H.Taniura,C.-H.Kuo,Y.Hayashi and N.Miki: "Purification and characterization of a receptor for neurit outgrowth factor (NOF)-Possible involvement of NOF-receptor in the axonal outgrowth from developing retinas." J.Cell Biol.112. 313-322 (1991)
[Publications] Y.Uchida,K.Takio,T.Titani,Y.Ihara and M.Tomonaga: "The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallotheionein-like protein." Neuron. 7. 337-347 (1991)
[Publications] T.Kirino,Y.Tsujita and A.Tamura: "Induced tolerance to ischemia in gerbil hippocampal neurons." J.Cereb Bkiid Flow Metab.11. 299-307 (1991)
[Publications] H.Kamiya,S.Sawada and C.Yamamoto: "Persistent enhancement of transmitter release accompanying long-term potentiation in the guinea pig hippocampus." Neurosci,Lett.130. 259-262 (1991)
[Publications] Yoshikai S: "Genomic organization of the human amyloid beta protein precursor gene." Gene. 102. 291-292 (1991)
[Publications] Yamada Y: "Expression of Alzheimer amyloid beta protein precursor gene in neuronal cell." Gerontology. 37. 24-30 (1991)
[Publications] Naruse S: "Mis-sense mutation Val-Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease." Lancet. 337. 978-979 (1991)
[Publications] Yoshioka K: "717 Val-Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups." B.B.R.C.178. 1141-1146 (1991)
[Publications] Ito T: "An improved system for physical selection of linking clones:Isolation of Sfi I linking clones from a chromosome 21-specific library." Genomics. 9. 707-712 (1991)
[Publications] 宮武正: "アルツハイマ-病の原因を探る" 文部省重点領域研究「脳の老化機構に関する分子細胞生物学的研究」班事務局, 141 (1991)

1991 Fiscal Year Annual Research Report

脳の老化機構に関する分子細胞生物学的研究

Principal Investigator

宮武 正 東京医科歯科大学, 医学部・神経内科, 教授 (50048998)

Research Products

[Publications] Shin RW: "Hydrated autoclave pretreatment enhances tau immunoreactivity in formalin-fixed normal and Alzheimer's disease brain tissues." Lab.Invest.64. 693-702 (1991)

[Publications] Mori M: "Jc virus detection by in situ hybridization in brain tissue from elderly patient." Ann.Neurol.29. 428-432 (1991)

[Publications] Kuwabara T: "Study on the erythrocytes from myotonic dystrophy with multinuclear NMR." Muscle Nerve. 14. 57-63 (1991)

[Publications] S.Inagaki,H.Takagi,K.Suzuki,F.Akai and N.Taniguchi: "Intense immunoreactivity for Mn-superoxide dismutase(Mn-SOD) in cholinergic and non-cholinergic neurons in the rat basal forebrain." Brain Research. 541. 354-357 (1991)

[Publications] R.Tamiya,M.Hanada,S.Inagaki and H.Takagi: "Synaptic relation between neuropeptide Y axons and cholinergic neurons in the rat diagonal band of Broca." Neuroscience Letters. 122. 64-66 (1991)

[Publications] T.Araki and M.Tohyama: "Regionーspecific expression of GABA_A receptor α3 and α4 subunits mRNAs in the rat brain." Molecular Brain Research. 12. 293-314 (1992)

[Publications] J.H.Zhang,M.Sato and M.Tohyama: "Regionーspecific expression of the mRNAs encoding β subunits (β1,β2 and β3) of GABA_A receptor in the rat brain." The Journal of Comparative Neurology. 303. 637-657 (1991)

[Publications] H.Taniura,C.-H.Kuo,Y.Hayashi and N.Miki: "Purification and characterization of a receptor for neurit outgrowth factor (NOF)-Possible involvement of NOF-receptor in the axonal outgrowth from developing retinas." J.Cell Biol.112. 313-322 (1991)

[Publications] Y.Uchida,K.Takio,T.Titani,Y.Ihara and M.Tomonaga: "The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallotheionein-like protein." Neuron. 7. 337-347 (1991)

[Publications] T.Kirino,Y.Tsujita and A.Tamura: "Induced tolerance to ischemia in gerbil hippocampal neurons." J.Cereb Bkiid Flow Metab.11. 299-307 (1991)

[Publications] H.Kamiya,S.Sawada and C.Yamamoto: "Persistent enhancement of transmitter release accompanying long-term potentiation in the guinea pig hippocampus." Neurosci,Lett.130. 259-262 (1991)

[Publications] Yoshikai S: "Genomic organization of the human amyloid beta protein precursor gene." Gene. 102. 291-292 (1991)

[Publications] Yamada Y: "Expression of Alzheimer amyloid beta protein precursor gene in neuronal cell." Gerontology. 37. 24-30 (1991)

[Publications] Naruse S: "Mis-sense mutation Val-Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease." Lancet. 337. 978-979 (1991)

[Publications] Yoshioka K: "717 Val-Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups." B.B.R.C.178. 1141-1146 (1991)

[Publications] Ito T: "An improved system for physical selection of linking clones:Isolation of Sfi I linking clones from a chromosome 21-specific library." Genomics. 9. 707-712 (1991)

[Publications] 宮武 正: "アルツハイマ-病の原因を探る" 文部省重点領域研究「脳の老化機構に関する分子細胞生物学的研究」班事務局, 141 (1991)

宮武正東京医科歯科大学, 医学部・神経内科, 教授 (50048998)

[Publications] 宮武正: "アルツハイマ-病の原因を探る" 文部省重点領域研究「脳の老化機構に関する分子細胞生物学的研究」班事務局, 141 (1991)