Studies on degradation of amyloid beta-protein by angiotensin-converting enzyme (ACE)

• Project/Area Number: 19300138
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Institute for Longevity Sciences,NCGG
• Principal Investigator: MICHIKAWA Makoto National Institute for Longevity Sciences,NCGG, アルツハイマー病研究部, 部長 (40270912)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2007: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
• Keywords: 精神・神経疾患の病態と治療 / アルツハイマー病 / 蛋白分解酵素 / 治療 / アンギオテンシン変換酵素 / アミロイドベータ蛋白

Research Abstract

アルツハイマー病の病因分子であるamyloid β蛋白(Aβ)の分解酵素であるACEの脳内Aβ沈着に及ぼす影響を解析し、ACEが脳内でAβの分解やAβ42をAβ40に変換する働きをしていることを明らかにした。また、ACEにある2つの主要ドメイン機能は、それぞれ異なる基質(アンギオテンシンIならびにAβ)に対して別の作用を持つことを明らかにした。

Research Products

• [Journal Article] Angiotensin-converting enzyme as a potential target for treatment of Alzheimer's disease : Inhibition or activation? (2009)
  • Author(s): Zou K, Michikawa M
  • Journal Title: Rev Neurosci, 19 Pages: 203-212
  • Peer Reviewed
• [Journal Article] New amyloid plaques or a game of hide-and-seek? (2008)
  • Author(s): Zou K, Maeda T, Michikawa M, Komano H
  • Journal Title: Int J Biol Sci 4 Pages: 200-201
• [Journal Article] Angiotensin-converting enzyme as a potential target for treatment of Alzheimer's disease : Inhibition or activation? (2008)
  • Author(s): Zou K, Michikawa M
  • Journal Title: Rev Neurosci 19 Pages: 203-212
• [Journal Article] Novel role of presenilins in maturation and transport of integrin β1 (2008)
  • Author(s): Zou K, Hosono T, Nakamura T, Shiraishi H, Naeda T, Komano H, Yanagisawa K, Michikawa M
  • Journal Title: Biochemistry 47(11) Pages: 3370-3378
• [Journal Article] Novel role of presenilins in maturation and transport of integrin β1 (2008)
  • Author(s): Zou K, Hosono T, Nakamura T, Shiraishi H, Maeda T, Komano H, Yanagisawa K, Michikawa M
  • Journal Title: Biochemistry 47 Pages: 3370-3378
  • Peer Reviewed
• [Journal Article] New amyloid plaques or a game of hide-and-seek? (2008)
  • Author(s): Zou K, Maeda T, Michikawa M, Komano H
  • Journal Title: Int J Biol Sci, 4 Pages: 200-201
  • Peer Reviewed
• [Journal Article] アルツハイマー病とスタチン (2008)
  • Author(s): 道川誠
  • Journal Title: BioClinica 23 Pages: 52-57
• [Journal Article] Alzheimer 病研究の進歩と治療戦略 (2008)
  • Author(s): 道川誠
  • Journal Title: 医学のあゆみ「老化と疾患」-病態の理解と診断・治療の進歩 別冊 Pages: 39-46
• [Journal Article] アポリポ蛋白E (2008)
  • Author(s): 道川誠
  • Journal Title: 日本臨床 66 Pages: 156-162
• [Journal Article] コレステロール代謝とアルツハイマー病 (2008)
  • Author(s): 道川誠
  • Journal Title: 臨床検査 52 Pages: 325-329
• [Journal Article] アポリポ蛋白Eはアミロイド蛋白βの分解を促進させる (2008)
  • Author(s): 道川誠
  • Journal Title: Cognition and Dementia 7 Pages: 58-59
• [Journal Article] Novel role of presenilins in maturation and transport of integrin β1. (2008)
  • Author(s): Zou K, Hosono T, Nakamura T, Shiraishi H, Maeda T, Komano H, Yanagisawa K, Michikawa M.
  • Journal Title: Biochemistry 47 Pages: 3370-3378
  • Peer Reviewed
• [Journal Article] Angiotensin-converting enzyme converts amyloid β-protein1-42 (Aβ(1-42)) to Aβ(1-40), and its inhibition enhances brain Aβ deposition (2007)
  • Author(s): Zou K, Yamaguchi H, Akatsu H, Sakamoto T, Ko M, Mizoguchi K, Gong JS, Yu W, Yamamoto T, Kosaka K, Yanagisawa K, Michikawa M
  • Journal Title: J Neurosci. 27(32) Pages: 8628-8635
• [Journal Article] Novel action of apolipoprotein E (ApoE) : ApoE isoform specifically inhibits lipid-partide-mediated cholesterol release from neurons (2007)
  • Author(s): Gong JS, Morita SY, Kobayashi M, Handa T, Fujita SC, Yanagisawa K, Michikawa M
  • Journal Title: Mol Neurodegener 2 Pages: 9-9
• [Journal Article] A ganglioside-induced toxic soluble Aβ assembly. Its enhanced formation from Aβ bearing the Arctic mutation (2007)
  • Author(s): amamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Maruyama W, Michikawa M, Yanagisawa K
  • Journal Title: J Biol Chem. 282(4) Pages: 2646-2655
• [Journal Article] Angiotensin-converting enzyme converts amyloid β-protein1-42(Aβ(1-42))to Aβ(1-40), and its inhibition enhances brain Aβ deposition (2007)
  • Author(s): Zou K, Yamaguchi H, Akatsu H, Sakamoto T, Ko M, Mizoguchi K, Gong JS, Yu W, Yamamoto T, Kosaka K, Yanagisawa K, Michikawa M.
  • Journal Title: J Neurosci 27(32) Pages: 8628-8635
  • Peer Reviewed
• [Journal Article] Novel action of apolipoprotein E(ApoE) : ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons. (2007)
  • Author(s): Gong JS, Morita SY, Kobayashi M, Handa T, Fujita SC, Yanagisawa K, Michikawa M.
  • Journal Title: Mol Neurodegeneration 2:9 Pages: 1-10
  • Peer Reviewed
• [Journal Article] A ganglioside-induced toxic soluble Aβ assembly. Its enhanced formation from Aβ bearing the Arctic mutation. (2007)
  • Author(s): Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takashima A, Maruyama W, Michikawa M, Yanagisawa K
  • Journal Title: J Biol Chem 282(4) Pages: 2646-2655
  • Peer Reviewed
• [Journal Article] Mechanism underlying apolipoprotein E isoform-dependent lipid efflux from neural cells in culture
  • Author(s): Minagawa K, Gong J-S, Jung C-G, Watanabe A, Lund-Katz S, Phillips M C, Saito H, Michikawa M
  • Journal Title: J Neurosci Res (印刷中)
  • Peer Reviewed
• [Presentation] アルツハイマー病って何? -その予防と治療法開発の最前線- (2008)
  • Author(s): 道川誠
  • Organizer: あいち健康長寿産業クラスター形成事業 国立長寿医療センター県民講座
  • Place of Presentation: 東浦町
  • Year and Date: 2008-12-02
• [Presentation] Aβ代謝における脂質の意義-Cholesterol paradoxを紐解く一考察 (2008)
  • Author(s): 道川誠
  • Organizer: 第27回日本認知症学会、ワークショップII
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-11
• [Presentation] ホモシステインはApoE3によるHDL産生を阻害する (2008)
  • Author(s): Minagawa H, Gong J-S, Lund-Katz S, Phillips M, Saito H, Michikawa M
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-10
• [Presentation] アルツハイマー病患者での血中Aβとアンギオテンシン変換酵素活性相関解析 (2008)
  • Author(s): 赤津裕康, 小川倫弘, 兼坂岳志, 山本孝之, 道川誠
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-10
• [Presentation] Presenilin regulates the maturation of membrane (2008)
  • Author(s): Zou Kun, 細野崇, 中村俊行, 白石博久, 前田智司, 駒野宏人, 道川誠
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-10
• [Presentation] Presenilin regulates the maturation of membrane proteinsin opposite directins (2008)
  • Author(s): Zou Kun, 細野崇, 中村俊行, 白石博久, 前田智司, 駒野宏人, 道川誠
  • Organizer: 第27回日本認知症学会
  • Place of Presentation: 前橋
  • Year and Date: 2008-10-10
• [Presentation] Inhibitory effect of homocysteine on ApoE3-mediated cholesterol efflux from cultured astrocytes (2008)
  • Author(s): Minagawa H, Gong J-S, Lund-Katz S, Phillips M, Saito H, Michikawa M
  • Organizer: 第51回日本神経化学会総会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [Presentation] 脂質代謝と神経変性疾患-その現状と未来への展望 育成セミナー講義 (2008)
  • Author(s): 道川誠
  • Organizer: 第51回日本神経化学会総会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [Presentation] アルツハイマー病の病態生理と治療戦略 (2008)
  • Author(s): 道川誠
  • Organizer: 名古屋市立大学大学院薬学研究科講義
  • Place of Presentation: 名古屋市立大学
  • Year and Date: 2008-06-25
• [Presentation] Cholesterol Metabolism in the Central Nervous System and Alzheimer's Disease (2008)
  • Author(s): Michikawa M.
  • Organizer: Pan-Pacific International Partnership Conference on Pharmaceutical and Life Sciences (The 4th US-Japan Joint Conference)
  • Place of Presentation: 名古屋市立大学水野ホール, 名古屋
  • Year and Date: 2008-02-23
• [Presentation] 遺伝子多型で判断できるアルツハイマー病になりやすい人、なりにくい人 (2008)
  • Author(s): 源川博久, 道川誠
  • Organizer: ゲノム広場2008 in 名古屋(主催 : 文部科学省科学研究費 特定領域ゲノム4領域)
  • Place of Presentation: 名古屋大学豊田講堂, 名古屋
• [Presentation] Angiotensin-concerting enzyme converts Abetal-42 to Abetal-40 and its inhibition enhances brain Abeta deposition (2007)
  • Author(s): Zou K, Yamaguchi H, Akatsu H, Sakamoto T, Ko M, Mizoguchi K, Gong JS, Yu W, Yamamoto T, Koska K, Komano H, Yanagisawa K, Michikawa M
  • Organizer: 第30回日本分子生物学会年会および 第80回日本生化学会大会、シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 脳内コレステロール代謝制御とその破綻に起因する神経細胞障害 (2007)
  • Author(s): 道川 誠
  • Organizer: 第30回日本分子生物学会年会および 第80回日本生化学会大会、シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] ER stress inducible protein, Herp, is involved in the degradation of the cofactor of gamma-secretase complex. (2007)
  • Author(s): Marutani T, Maeda T, Kokame K, Zou K, Michikawa M, Komano H.
  • Organizer: 第30回日本分子生物学会年会および 第80回日本生化学会大会、シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Angiotensin-converting enzyme converts Aβ1-42 to Aβ1-40 and its inhibition enhances brain Aβ deposition. (2007)
  • Author(s): K. Zou, H. Yamagucih, H. Akatsu T. Sakamoto, M. Ko, K. Mizoguchi, J.-S. Gong, W. Yu, T. Yamamoto, K. Kosaka, K. Yanagisawa, Michikawa M
  • Organizer: 北米神経科学会
  • Place of Presentation: サンジエゴ、米国
  • Year and Date: 2007-11-06
• [Presentation] Mechanism underlying apolipoprotein e isoform-dependent lipid efflux from cultured neurons (2007)
  • Author(s): Minagawa H. Watanabe A, Gong J.-S., Zou K, Nakamura T. Lind-Katz S. Phillips MC, Saito H, Michikawa M.
  • Organizer: 北米神経科学会
  • Place of Presentation: サンジエゴ、米国
  • Year and Date: 2007-11-06
• [Presentation] Transforming growth factor-betal associates with apoE-containing high-density lipoproteins : implications for neurodegeneration (2007)
  • Author(s): Tesseur I. C. Huang Y, Corn GJ, Gong J.-S. Yanagisawa K. Michikawa M, Weisgraber, Wyss-Coray T.
  • Organizer: 北米神経科学会
  • Place of Presentation: サンジエゴ、米国
  • Year and Date: 2007-11-06
• [Presentation] A ganglioside-induced soluble Abeta assembly causes neuronal death through NGF receptors (2007)
  • Author(s): Yamamoto N, Matsubara E, Maeda S, Minagawa H, Takeshita A. Michikawa M, Yanagisawa K
  • Organizer: 北米神経科学会
  • Place of Presentation: サンジエゴ、米国
  • Year and Date: 2007-11-05
• [Presentation] Characterization of therapeutic antibody against Aβ oligomers for Alzheimer's disease (2007)
  • Author(s): H. Sun, Y. Okamoto, T. Kawarabayashi, T. Yokoseki M. Shibata, M. Morishimas, Y. Saito, S. Murayama, Y. Ihara, M. Shoji M. M Michikawa, E. Matsubara
  • Organizer: 北米神経科学会
  • Place of Presentation: サンジエゴ、米国
  • Year and Date: 2007-11-05
• [Presentation] Apolipoprotein E-isoform-specific modulation of cholesterol metabolism in neurons (2007)
  • Author(s): Michikawa M.
  • Organizer: 日本神経化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-12
• [Presentation] Isoform-dependnent effect of apolipoprotein E on cholesterol efflux. (2007)
  • Author(s): Minagawa H, Gong J-S, Nakamura T, Zou K, Lund-Katz S, Phillips M, Saito H, Michikawa M
  • Organizer: 日本神経化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-11
• [Presentation] アルツハイマー病の分子メカニズムと治療戦略
  • Author(s): 道川誠
  • Organizer: 神経内科認知症研究会
  • Place of Presentation: 名古屋