Analysis of amino acid imbalance underlying Alzheimer's disease

• Project/Area Number: 20300245
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Eating habits, studies on eating habits
• Research Institution: Gifu University
• Principal Investigator: NAKAGAWA Toshiyuki Gifu University, 医学系研究科, 教授 (00271502)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2009: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2008: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
• Keywords: アルツハイマー病 / ガンマ-セクレターゼ / プレセニリン / 小胞体ストレス / オートファジー / ATF4 / アミノ酸 / food intake experiment / レスベラトロール / GCN2 / 加齢 / ロイシン / ブレセニリン / ガンマセクレターゼ / アミノ酸センサー

Research Abstract

To explore novel therapeutic and preventive interventions for Alzheimer's disease, I nvestigated the molecular mechanism of amyloid-β production. I found that (1) the expression of proteins related to signaling molecules for autophagy was dynamically changed in the mouse brain during ageing, (2) GCN2-eIF2α phosphorylation-ATF4 cascade was a molecular mechanism for the upregulation of amyloid-β production through affecting γ-secretase activity.

Research Products

• [Journal Article] Cayman Ataxia-Related Protein is a Presynapse-Specific Caspase-3 Substrate. (2011)
  • Author(s): Itoh M, Li S, Ohta K, Yamada A, Hayakawa-Yano Y, Ueda M, Hida Y, Suzuki Y, Ohta E, Mizuno A, Banno Y, Nakagawa T.
  • Journal Title: Neurochemical Research. DOI 10.1007
  • Peer Reviewed
• [Journal Article] Cayman Ataxia-Related Protein is a Presynapse-Specific Caspase-3 Substrate (2011)
  • Author(s): Itoh Masamori
  • Journal Title: Neurochemical Research
  • Peer Reviewed
• [Journal Article] Autophagy impairment stimulates PS1 expression and β-secretase activity. (2010)
  • Author(s): Ohta K, Mizuno A, Ueda M, Li S, Suzuki Y, Hida Y, Hayakawa-Yano Y, Itoh M, Ohta E, Kobori M, Nakagawa T.
  • Journal Title: Autophagy. 6 Pages: 345-352
  • Peer Reviewed
• [Journal Article] Autophagy impairment stimulates PSI expression and gamma-secretase activity (2010)
  • Author(s): Kazunori Ohta
  • Journal Title: Autophagy 6 Pages: 345-352
  • Peer Reviewed
• [Journal Article] An alternative spliced mouse presenilin-2 Mrna encodes a novel ・-secretase inhibitor. (2009)
  • Author(s): Suzuki Y, Ohta K, Itoh M, Sakoh-Sumitomo Y, Mitsuda T, Ueda M, Hayakawa-Yano Y, Li S, Hida Y, Inuzuka T, Jung YK, Nakagawa T.
  • Journal Title: FEBS letters. 583 Pages: 1403-1408
  • Peer Reviewed
• [Journal Article] An alternative spliced mouse presenilin-2 mRNA encodes a novel gamma-secretase inhibitor. (2009)
  • Author(s): Yoshinori Suzuki
  • Journal Title: FEBS Letters 583 Pages: 1403-1408
  • Peer Reviewed
• [Journal Article] E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated Aβ neurotoxicity. (2008)
  • Author(s): Song S, Lee H, Kam TI, Tai ML, Lee JY, Noh JY, Shim SM, Seo SJ, Kong YY, Nakagawa T, Chung CW, Choi DY, Oubrahim H, Jung YK.
  • Journal Title: J Cell Biol. 182 Pages: 675-684
  • Peer Reviewed
• [Journal Article] E2-25K/llip-2 regulates caspase-12in ER stress - mediated Aβ neurotoxicity (2008)
  • Author(s): Sungmin Song
  • Journal Title: J. Cell Biol. 182 Pages: 675-684
  • Peer Reviewed
• [Presentation] Autophagy impairment leads to activation of gamma secretase through GCN2 (2010)
  • Author(s): 太田和徳, 水野彰人, 上田昌史, 李詩沫, 鈴木欣宏, 樋田陽子, 早川-矢野佳芳, 伊藤正徳, 太田瑛里, 中川敏幸
  • Organizer: 米国神経科学学会
  • Place of Presentation: Diego, USA
  • Year and Date: 2010-11-17
• [Presentation] Autophagy impairment leads to activation of gamma-secretase through GCN2. (2010)
  • Author(s): 中川敏幸
  • Organizer: 米国神経科学学会
  • Place of Presentation: サンディエゴ,アメリカ
  • Year and Date: 2010-11-17
• [Presentation] オートファジーの機能低下がもたらすGCN2 を介したガンマセクレターゼ活性亢進機構の解明 (2010)
  • Author(s): 太田和徳, 水野彰人, 上田昌史, 李詩沫, 鈴木欣宏, 樋田陽子, 早川-矢野佳芳, 伊藤正徳, 太田瑛里, 小堀真珠子, 中川敏幸
  • Organizer: Neuro2010
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2010-09-02
• [Presentation] Disruption of the endoplasmic reticulum by polyglutamine expansion induces Apaf-1-dependent, activation of caspase-7. (2009)
  • Author(s): 上田昌史, 李詩沫, 伊藤正徳, 樋田陽子, 早川-矢野佳芳, 鈴木欣宏, 太田和徳, 太田瑛里, 水野彰人, 中川敏幸
  • Organizer: 米国神経科学学会
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-10-20
• [Presentation] Disruption of the endoplasmic reticulum by polyglutamine expansion induces Apaf-1-dependent, activation of caspase-7. (2009)
  • Author(s): 中川敏幸
  • Organizer: 米国神経科学学会
  • Place of Presentation: シカゴ,アメリカ
  • Year and Date: 2009-10-20
• [Presentation] Disruption of the endoplasmic reticulum leads to Baxand Apaf-1-dependent activation of caspase-7. (2009)
  • Author(s): 上田昌史, 李詩沫, 早川-矢野佳芳, 太田和徳, 伊藤正徳, 樋田陽子, 太田瑛里, 水野彰人, 中川敏幸
  • Organizer: CELL DEATH Cold Spring Harbor Laboratory Meeting
  • Place of Presentation: New York, USA
  • Year and Date: 2009-10-08
• [Presentation] The novel splicing isoform of mouse presenilin-2 interrupts γ-secretase complex, inhibiting its activity. (2008)
  • Author(s): Suzuki Y, Ohta K, Itoh M, Ueda M, Li S, Hida Y, Sakoh-Sumitomo Y, Mitsuda T, Hayakawa-Yano Y, Inuzuka T, Nakagawa T
  • Organizer: 米国神経科学学会
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2008-11-17
• [Presentation] The novel splicing isoforni of mouse presenilin-2 inlerrupts γ-secrctase complex, inhibiting its activity (2008)
  • Author(s): 中川敏幸
  • Organizer: 米国神経科学学会
  • Place of Presentation: ワシントンDC, アメリカ
  • Year and Date: 2008-11-17
• [Presentation] 前シナプスに局在するCayman 運動失調症原因タンパク質(Caytaxin)の機能発現におけるCaspase-3の役割 (2008)
  • Author(s): 伊藤正徳, 李詩沫, 上田昌史, 太田和徳, 鈴木欣宏, 樋田陽子, 中川敏幸
  • Organizer: BMB2008
  • Place of Presentation: 神戸
• [Presentation] プレセニリン発現制御におけるオートファジーの役割の解明 (2008)
  • Author(s): 太田和徳, 鈴木欣宏, 伊藤正徳, 李詩沫, 上田昌史, 樋田陽子, 中川敏幸
  • Organizer: BMB2008
  • Place of Presentation: 神戸
• [Presentation] ガンマ‐セクレターゼ活性を制御する新規プレセニリン2 アイソフォームの解析 (2008)
  • Author(s): 鈴木欣宏, 太田和徳, 伊藤正徳, 上田昌史, 李詩沫, 樋田陽子, 酒向ゆかり, 光田輝彦, 犬塚貴, 中川敏幸
  • Organizer: BMB2008
  • Place of Presentation: 神戸
• [Remarks] ホームページ等
  • URL: http://www1.gifu-u.ac.jp/~neurobio/
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~neurobio/