1990 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	02240102
Research Institution	Niigata University
Principal Investigator	宮武正新潟大学, 脳研究所, 教授 (50048998)
Co-Investigator(Kenkyū-buntansha)	高久史麿国立病院医療センター, 院長 (40048955) 榊佳之九州大学, 遺伝情報実験施設, 教授 (10112327) 高木宏大阪市立大学, 医学部, 教授 (30163174) 三木直正大阪大学, 医学部, 教授 (40094445) 立石潤九州大学, 医学部, 教授 (70033305)
Keywords	アルツハイマ-病 / アミロイド前駆蛋白 / 神経原線維変化 / 神経抑制因子(GIF) / アルツハイマ-遺伝子
Research Abstract	本年度もアルツハイマ-病(AD)の病因解明に向けて、いくつかの研究の進展をみた。その主な点は以下のとおりである。ADに見られる神経原線維変化(PHF)の主要な構成成分であるタウについては、これが胎児型であること、そしてタウのリン酸化部位としてC末端の2つのフラグメントが示された。また、このリン酸化を触媒する2種類のキナ-ゼが同定された。β/A4とアミロイドに関しては、その前駆タンパク(APP)を中心に研究が推進され、APPは神経細胞のみならず副腎髄質細胞、精巣などにも分布することが示された。APPには3つの分子種が存在することが知られていたが、その中のAPP695が神経細胞に特異的であることが明らかになった。APP遺伝子の発現機序が検討された。 AD脳で出現する各種の神経成長因子(NGF)や突起伸展因子(NOF)について検討され、今回、新らたに成長抑制因子(GIF)が発見された。そしてこのGIFがAD脳では欠如していること、これがメタルチオネインとホモロジ-が高いことが示された。そして更にこのGIFのcDNAが分離され、ADの研究に大きな指針が与えられた。家族性アルツハイマ-病(FAD)については本邦家系の集積が行われ、遺伝子連鎖解析の準備が開始された。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] K.Maruyama,K.Terakado,M.Usami&K.Yoshikawa: "Formation of amyloidーlike fibrils in COS cells overexprossing part of the Alzheimer amyloid protein precursqr" NATURE. 347. 566-569 (1990)
[Publications] H.Kido,A.Fukutomi,J.Schilling,Yu Wang,B.Cordell&N.Katunuma: "Proteaseーspecificity of kunitz inhibitor domain of alzheimer's disease amyloid protein precursor" Biochem.Biophys.Res.commun.167. 716-721 (1990)
[Publications] M.Xu,T.Yamamoto and T.Kato: "In vivo striatal dopamine release by M1 muscarinic receptors is induced by activation of protein kinase C" Neurochem. 54. 1917-1919 (1990)
[Publications] N.Nakahara,N.Fujise and F.Mizobe: "Central muscarinic activities of a M1ーselective agonist:Preferential effect on reversal of amnesia" Brain Research. 507. 172-175 (1990)
[Publications] 内田洋子: "アルツハイマ-病と神経栄養因子" 神経進歩. 34. 651-659 (1990)
[Publications] Hasegawa M.Arai T.Ihara Y.: "Immunochemical evidence that fragments of phosphorylated MAP5(MAP1B)are bound to neurofibrillary tangles in Alzheimer's disease" Neuron. 36. 15-24 (1990)
[Publications] F.Hosoda,S.Nishimura,H.Uchida and M.Ohki: "An F factor based cloning system for lare DNA fragments" Nucleic Acids Res.18. 3863-3869 (1990)
[Publications] H.Akiyama,T.Kaneko,N.Mizuno and P.H.McGeer: "Distribution of phosphateーactivated glutaminase in the human cerebral cortex" J.compara.neurol. 297. 239-252 (1990)
[Publications] S.Yoshikai,H.Sasaki,K.Dohーura,H.Furuya and Y.Sakaki: "Genomic organization of the human amyloid betaーprotein precursor gene" Gene. 87. 257-263 (1990)
[Publications] R.Takeuchi,K.Murase,Y.Furukawa,S.Furukawa and K.Hayashi: "Stimulation of nerve growth factor synthesis/secretion by 1,4ーbenzoquinone and its derivatives in cultured mouse astroglial cells" FEBS Lett. 261. 63-66 (1990)
[Publications] F.Kametani,P.Huga,K.Tanaka,T.Ishii: "Amyloid beta protein precursor(APP) of cultured cells:secretory and nonーsecretory forms of APP" J.Neurol.Sci. 97. 43-52 (1990)
[Publications] N.Kitaguchi,Y.Tokushima,K.Oishi,Y.Takahashi,S.Shiojiri,S.Nakamura,S.Tanaka,R.Kodaira,and H.Ito: "Determination of amyloid βーprotein precursors haboring aetive form of proteinase inhibitor domains in cerebrospinal fluid of Alzheimer's disease patients by trypsinーantibody Sandwich ELISA" Biochem.Biophys.Res.commun. 166. 1453-1459 (1990)
[Publications] Akai,H.,Maeda,M.,Suzuki,K.,Inagaki,S.,Takagi,H.and Taniguchi,N.: "Immunohistochemical localization of manganese superoxide dismutase (MnーSOD)in the hippocampus of the rat." Neuroscience Letters. 115. 19-23 (1990)
[Publications] A.Kose,A.Ito,N.Saito and C.Tanaka: "Electoron microscopic localization of γ and βIIーsubspecies of protein kinase C in rat hippocampus." Brain Res.518. 209-217 (1990)
[Publications] N.Takei,H.Tsukui,K.Kumakura and H.Hatanaka: "Monitoring of acetylcholine released from postnatal rat basal forebrain cholinergic neurons cultured on membrane filter by cell bed perfusion system and HPLCーECD." Exp.Neurol.108. 229-231 (1990)
[Publications] S.Ishiura,T.Nishikawa,T.Tsukahara,H.Itoh,K.Suzuki,H.Sugita: "Distribution of amyloid A4 generating enzymes in the rat brain tissue" Biochim.Biophys.Acta. (1990)
[Publications] Ishizuka,N.,Amaral,D.G.Weber,J.: "Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat" J.Comp.Neurol.295. 423-439 (1990)
[Publications] 朝長正徳、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, 117 (1990)
[Publications] T.Miyatake,D.J.Selkoe and Y.Ihara: "Molecular biology and genetics of Alzheimer's desease" Excerpta medica,Amsterdam, 288 (1990)

1990 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 新潟大学, 脳研究所, 教授 (50048998)

Research Products

[Publications] K.Maruyama,K.Terakado,M.Usami&K.Yoshikawa: "Formation of amyloidーlike fibrils in COS cells overexprossing part of the Alzheimer amyloid protein precursqr" NATURE. 347. 566-569 (1990)

[Publications] H.Kido,A.Fukutomi,J.Schilling,Yu Wang,B.Cordell&N.Katunuma: "Proteaseーspecificity of kunitz inhibitor domain of alzheimer's disease amyloid protein precursor" Biochem.Biophys.Res.commun.167. 716-721 (1990)

[Publications] M.Xu,T.Yamamoto and T.Kato: "In vivo striatal dopamine release by M1 muscarinic receptors is induced by activation of protein kinase C" Neurochem. 54. 1917-1919 (1990)

[Publications] N.Nakahara,N.Fujise and F.Mizobe: "Central muscarinic activities of a M1ーselective agonist:Preferential effect on reversal of amnesia" Brain Research. 507. 172-175 (1990)

[Publications] 内田 洋子: "アルツハイマ-病と神経栄養因子" 神経進歩. 34. 651-659 (1990)

[Publications] Hasegawa M.Arai T.Ihara Y.: "Immunochemical evidence that fragments of phosphorylated MAP5(MAP1B)are bound to neurofibrillary tangles in Alzheimer's disease" Neuron. 36. 15-24 (1990)

[Publications] F.Hosoda,S.Nishimura,H.Uchida and M.Ohki: "An F factor based cloning system for lare DNA fragments" Nucleic Acids Res.18. 3863-3869 (1990)

[Publications] H.Akiyama,T.Kaneko,N.Mizuno and P.H.McGeer: "Distribution of phosphateーactivated glutaminase in the human cerebral cortex" J.compara.neurol. 297. 239-252 (1990)

[Publications] S.Yoshikai,H.Sasaki,K.Dohーura,H.Furuya and Y.Sakaki: "Genomic organization of the human amyloid betaーprotein precursor gene" Gene. 87. 257-263 (1990)

[Publications] R.Takeuchi,K.Murase,Y.Furukawa,S.Furukawa and K.Hayashi: "Stimulation of nerve growth factor synthesis/secretion by 1,4ーbenzoquinone and its derivatives in cultured mouse astroglial cells" FEBS Lett. 261. 63-66 (1990)

[Publications] F.Kametani,P.Huga,K.Tanaka,T.Ishii: "Amyloid beta protein precursor(APP) of cultured cells:secretory and nonーsecretory forms of APP" J.Neurol.Sci. 97. 43-52 (1990)

[Publications] Akai,H.,Maeda,M.,Suzuki,K.,Inagaki,S.,Takagi,H.and Taniguchi,N.: "Immunohistochemical localization of manganese superoxide dismutase (MnーSOD)in the hippocampus of the rat." Neuroscience Letters. 115. 19-23 (1990)

[Publications] A.Kose,A.Ito,N.Saito and C.Tanaka: "Electoron microscopic localization of γ and βIIーsubspecies of protein kinase C in rat hippocampus." Brain Res.518. 209-217 (1990)

[Publications] N.Takei,H.Tsukui,K.Kumakura and H.Hatanaka: "Monitoring of acetylcholine released from postnatal rat basal forebrain cholinergic neurons cultured on membrane filter by cell bed perfusion system and HPLCーECD." Exp.Neurol.108. 229-231 (1990)

[Publications] S.Ishiura,T.Nishikawa,T.Tsukahara,H.Itoh,K.Suzuki,H.Sugita: "Distribution of amyloid A4 generating enzymes in the rat brain tissue" Biochim.Biophys.Acta. (1990)

[Publications] Ishizuka,N.,Amaral,D.G.Weber,J.: "Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat" J.Comp.Neurol.295. 423-439 (1990)

[Publications] 朝長 正徳、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, 117 (1990)

[Publications] T.Miyatake,D.J.Selkoe and Y.Ihara: "Molecular biology and genetics of Alzheimer's desease" Excerpta medica,Amsterdam, 288 (1990)

宮武正新潟大学, 脳研究所, 教授 (50048998)

[Publications] 内田洋子: "アルツハイマ-病と神経栄養因子" 神経進歩. 34. 651-659 (1990)

[Publications] 朝長正徳、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, 117 (1990)