1996 Fiscal Year Annual Research Report

アルツハイマー病の原因遺伝子S182,E5-1遺伝子のβ蛋白分泌における役割

Research Project

Project/Area Number	08838003
Research Category	Grant-in-Aid for Scientific Research (C)
Section	時限
Research Institution	Gunma University
Principal Investigator	東海林幹夫群馬大学, 医学部・神経内科, 講師 (60171021)
Keywords	アルツハイマー病 / S182 / E5-1 / β蛋白
Research Abstract	平成8年度はヒト脳cDNA libraryからS182(presenilin-1)およびE5-1(presenilin-2)のcDNAをクローニングし,pCDNA3につなぎ,得られた全塩基配列のsequencingを行い確認した.misense primerをもちいて,presenilin-1 △A246E(FAD1),presenilin-1 △L286V(FAD2),presenilin-1 △M146L(FAD4),presenilin-1 △L392V(Borras Italian),presenilin-2 △N141I(VG-1),presenilin-2 △M239V(FLO)のそれぞれのmutant typeを作製し,pCDNA3につないで増殖させた.presenilin-1とpresenilin-2のそれぞれN末端,C末端15-23アミノ酸を合成し,ウサギに免疫し,特異抗体HS-N2とHS-Cを得た.wild type presenilin-1をCOS-7細胞に発現させると,43kDのfull lenghtのPS-1と28kDのN末端fragment,18kDのC末端fragmentと認めた.ヒト大脳のWestern blotでも同様の分子量のPS-1とその代謝分画を認めた.presenilin-2は50kDのfull lenghtのPS-1と30kDのN末端fragmentを認めた.ヒト大脳の免疫細胞化学ではPS-1は神経細胞胞体,神経突起に局在していた.AD脳ではHSN-2で老人斑アミロイドを染色し,HS-Cで神経原線維変化,dystrophic neurites,curly fibersが染色された.PS-1は神経細胞に局在するが,AD脳では老人斑および神経原線維変化の形成にも関与する可能性がある.次年度はPS-1/-2のそれぞれの代謝分画をN末端ペプチドシークエンスを行い確定するとともに,原因遺伝子の点特異変異がAβ分泌に及ぼす影響,特にAβ1-42の増加がみられるのかどうかを検討する.

Research Products
(6 results)

All Other

All Publications (6 results)

[Publications] Masaki Ikeda: "The clinical Phenotype of Two Misseuse Matatious in the Presenilin I Gene in Japanese Patieuts" Annals of Neuro logy. 40.6. 912-917 (1996)
[Publications] Eduardo M.Castaro: "The length of Acmyloid-β in Hereditory Cerehral Hemorlage with A cmyloidosis,Dotch Type" Journal of Biological Clemistry. 271. 32185-32191 (1996)
[Publications] Takeshi Kawarabayashi: "Accumlation of β-amyloid fihnils in pancreas of Transganic rmice" Neurobiol-Aging. 17. 215-222 (1996)
[Publications] Iizuka Tomomichi: "Amyloid beta-protein ending at The 43 is aminor companent of some diffuseplaguls in the Alzheimer's disease orain" Brain Res.702. 275-8 (1995)
[Publications] Iizuka Tomomichi: "Intracellular generation of amyloid beta-protein from amyloid beta-prctein precusor fragment by direct cleavage" Biochem-Biophys-Res-Corumun. 2・18. 238-42 (1996)
[Publications] Masashi Abe: "A presenilin-I mutation in a Japanese family with Alzheimeis disease and distiuctive abnormalities on cranial MRI" Neurology. (in press).

1996 Fiscal Year Annual Research Report

アルツハイマー病の原因遺伝子S182,E5-1遺伝子のβ蛋白分泌における役割

Principal Investigator

東海林 幹夫 群馬大学, 医学部・神経内科, 講師 (60171021)

Research Products

[Publications] Masaki Ikeda: "The clinical Phenotype of Two Misseuse Matatious in the Presenilin I Gene in Japanese Patieuts" Annals of Neuro logy. 40.6. 912-917 (1996)

[Publications] Eduardo M.Castaro: "The length of Acmyloid-β in Hereditory Cerehral Hemorlage with A cmyloidosis,Dotch Type" Journal of Biological Clemistry. 271. 32185-32191 (1996)

[Publications] Takeshi Kawarabayashi: "Accumlation of β-amyloid fihnils in pancreas of Transganic rmice" Neurobiol-Aging. 17. 215-222 (1996)

[Publications] Iizuka Tomomichi: "Amyloid beta-protein ending at The 43 is aminor companent of some diffuseplaguls in the Alzheimer's disease orain" Brain Res.702. 275-8 (1995)

[Publications] Iizuka Tomomichi: "Intracellular generation of amyloid beta-protein from amyloid beta-prctein precusor fragment by direct cleavage" Biochem-Biophys-Res-Corumun. 2・18. 238-42 (1996)

[Publications] Masashi Abe: "A presenilin-I mutation in a Japanese family with Alzheimeis disease and distiuctive abnormalities on cranial MRI" Neurology. (in press).

東海林幹夫群馬大学, 医学部・神経内科, 講師 (60171021)