Characterization of Abeta-like peptide other in brains of Alzheimer disease

• Project/Area Number: 19591352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka University
• Principal Investigator: MASAYASU Okochi Osaka University, 医学系研究科, 助教 (90335357)
• Co-Investigator(Kenkyū-buntansha): TAGAMI Shinji 大阪大学, 医学系研究科, 助教 (40362735) ; TAKEDA Masatoshi 大阪大学, 医学系研究科, 教授 (00179649)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アルツハイマー病 / アミロイドβ蛋白 / Notch1 / APLP1 / 老人斑 / 不溶性蛋白 / サロゲートマーカー

Research Abstract

我々は生理的に脳内に存在するアルツハイマー病Aβと同じ仕組みで放出されたAβ様ペプチドの凝集性などの性質を検討し、Aβとの異同を論じた。その結果、(i)Nβ、APL1βペプチドなどのAβ様ペプチド群がoligomerを形成するが、(ii)fibril形成しない。また、(iii)Aβ様ペプチド群はAβのoligomerやfibril形成を修飾せず、(iv)老人斑などへの集積性が小さく不溶性分画に含まれない。面白いことに、病原性Aβ42の比較的産生を増大させるプレセニリンの変異やγセクレターゼ修飾薬の添加はAβ様ペプチドのC末端にも同じように影響した。Aβを産生する生体内の仕組みはアルツハイマー病を起因するだけではなく、広く細胞の活動を支える役割があり、Notchシグナルのような機能が今後明らかになっていくと考えられる。

Research Products

• [Journal Article] Processes of beta-Amyloid and Intracellular Cytoplasmic Domain Generation by Presenilin/gamma-Secretase (2008)
  • Author(s): Tagami S, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M
  • Journal Title: Neurodegener Dis 5(3-4) Pages: 160-2
  • Peer Reviewed
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precision of S3 cleavage of Notch-1 (2008)
  • Author(s): Tagami S, Okochi M, Yanagida K, Ikuta A, Fukumori A, Matsumoto N, Ishizuka-Katsura Y, Nakayama T, Itoh N, Jiang J, Nishitomi K, Kamino K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Chiba S, Takeda M
  • Journal Title: Mol Cell Biol 28(1) Pages: 165-76
  • Peer Reviewed
• [Journal Article] Macrophage colony stimulating factor is associated with excretion of amyloid-β peptides from cerebrospinal fluid to peripheral blood (2008)
  • Author(s): Jiang, J., Okochi, M., Tagami, S., Nishitomi, K., Yanagida, K., Nakayama, T., Tatsumi, S.-I., Mori, K., Takeda, M
  • Journal Title: Psychogeriatrics Pages: 188-195
  • NAID: 10027274800
  • Peer Reviewed
• [Journal Article] Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C virus core protein and viral propagation (2008)
  • Author(s): Okamoto K, Mori Y, Komoda Y, Okamoto T, Okochi M, Takeda M, Suzuki T, Moriishi K, Matsuura Y
  • Journal Title: J Virol 82 Pages: 8349-8361
  • Peer Reviewed
• [Journal Article] Processes of beta-Amyloid and Intracellular Cytoplasmic Domain Generation by Presenilin/gamma-Secretase. (2008)
  • Author(s): Tagami S, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M.
  • Journal Title: Neurodegener Dis. 5(3-4) Pages: 160-2
  • Peer Reviewed
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precision of S3 cleavage of Notch-1. (2008)
  • Author(s): Tagami S, Okochi M, Yanagida K, Ikuta A, Fukumori A, Matsumoto N, Ishizuka-Katsura Y, Nakayama T, Itoh N, Jiang J, Nishitomi K, Kamino K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Chiba S, Takeda M
  • Journal Title: Mol Cell Biol. 28(1) Pages: 165-76
  • Peer Reviewed
• [Journal Article] Macrophage colony stimulating factor is associated with excretion of amyloid-β peptides from cerebrospinal fluid to peripheral blood (2008)
  • Author(s): Jiang, J., Okochi, M., Tagami, S., Nishitomi, K., Yanagida, K., Nakayama, T., Tatsumi, S. -I., Mori, K., Takeda, M.
  • Journal Title: Psychogeriatrics 8 Pages: 188-195
  • NAID: 10027274800
  • Peer Reviewed
• [Journal Article] Intramembrane processing by signal peptide peptidase regulates the membrane localization of hepatitis C viruscore protein and viral propagation. (2008)
  • Author(s): Okamoto K, Mori Y, Komoda Y, Okamoto T, Okochi M, Takeda M, Suzuki T, Moriishi K, Matsuura Y.
  • Journal Title: J Virol 82 Pages: 8349-8361
  • Peer Reviewed
• [Journal Article] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-1 (2008)
  • Author(s): Okochi, M., Tagami, S., Takeda, M.
  • Journal Title: Annual Report of Osaka University Academic Achievement 2007-2008 9 Pages: 94-94
  • Peer Reviewed
• [Journal Article] アルツハイマー病の薬物療法の実際 (2008)
  • Author(s): 大河内正康, 武田雅俊
  • Journal Title: カレントテラピー 26
• [Journal Article] Regulation of Notch signaling byd ynamic changes in the precision of S3 cleavage of Notch-1. (2008)
  • Author(s): Tagami S, Okochi M, Yanagida K, Ikuta A, Fukumori A, Matsumoto N, Ishizuka-Katsura Y, Nakayama T, Itoh N, Jiang J, Nishitomi K, Kamino K, Morihara T, Hashimoto R, Tanaka T, Kudo T, Chiba S, Takeda M
  • Journal Title: Mol Cell Biol. 28(1) Pages: 165-76
  • Peer Reviewed
• [Journal Article] Biological markers as outcome measures for Alzheimer's disease interventions--real problems and future possibilities (2007)
  • Author(s): Takeda M, Okochi M, Tagami S, Tanaka T, Kudo T
  • Journal Title: Int Psychogeriatr 19(3) Pages: 391-400
  • Peer Reviewed
• [Journal Article] Biological markers as outcome measures for Alzheimer's disease interve ntions-real problems and future possibilities. (2007)
  • Author(s): Takeda M, Okochi M, Tagami S, Tanaka T, Kudo T.
  • Journal Title: Int Psychogeriatr. 19(3) Pages: 391-400
  • Peer Reviewed
• [Presentation] Characterization of APLP1-derived Abeta-like peptide in brains of Alzheimer disease patients (2008)
  • Author(s): Okochi, M
  • Organizer: ICAD2008
  • Year and Date: 2008-07-24
• [Book] Regulation of Notch signaling by dynamic changes in the precision in S3 cleavage of Notch-1 (2008)
  • Author(s): Okochi, M., Tagami, S., Takeda, M
  • Total Pages: 94
  • Publisher: Annual Report of Osaka University Academic Achievement 2007-2008
• [Book] アルツハイマー病の薬物療法の実際 (2008)
  • Author(s): 大河内正康、武田雅俊
  • Publisher: カレントテラピー