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• Project/Area Number: 23591243
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto University
• Principal Investigator: UEMURA Kengo 京都大学, 医学(系)研究科(研究院), その他 (00378663)
• Co-Investigator(Kenkyū-buntansha): KINOSHITA Ayae 京都大学, 医学研究科, 教授 (80321610)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経科学 / 痴呆 / 脳・神経 / アルツハイマー病 / 神経変性疾患 / 国際情報交流（アメリカ） / アミロイド前駆体蛋白

Research Abstract

Our group demonstrated that N-cadherin expression facilitates cis-dimerization of APP. Moreover, N-cadherin expression led to increased production of Abeta as well as soluble APP beta, indicating that beta secretase mediated cleavage of APP is enhanced. Then we investigated whether copper alters the state of APP dimerization and how it affects APP metabolism. We demonstrated that copper enhanced APP dimerization and increased extracellular release of Abeta. Taken together, our results suggest that modulation of APP dimerization state could be one of mechanisms, which alters Abeta production.

Research Products

• [Journal Article] Copper enhances APP dimerization and promotes Aβproduction (2013)
  • Author(s): Noda Y, Asada M, Kubota M, Maesako M, Watanabe K, Uemura M, Kihara T, Shimohama S, Takahashi R, Kinoshita A, Uemura K
  • Journal Title: Neurosci Lett Volume: 547 Pages: 10-5
• [Journal Article] Copper enhances APP dimerization and promotes Aβ production. (2013)
  • Author(s): Noda Y, Asada M, Kubota M, Maesako M, Watanabe K, Uemura M, Kihara T, Shimohama S, Takahashi R, Kinoshita A, Uemura K.
  • Journal Title: Neurosci Lett Volume: 547 Pages: 10-15
  • Peer Reviewed
• [Journal Article] Gain of function by phosphorylation in Presenilin 1-mediated regulation of insulin signaling (2012)
  • Author(s): Maesako M, Uemura K, Kuzuya A, Sasaki K, Asada M, Watanabe K, Ando K, Kubota M, Akiyama H, Takahashi R, Kihara T, Shimohama S, Kinoshita A
  • Journal Title: J Neurochem Volume: 121(6) Pages: 964-73
• [Journal Article] Environmental enrichment ameliorated high fat diet-induced Aβdeposition and memory deficit in APP transgenic mice (2012)
  • Author(s): Maesako M, Uemura K, Kubota M, Kuzuya A, Sasaki K, Asada M, Watanabe K, Hayashida N, Ihara M, Ito H, ShimohamaS, Kihara T, Kinoshita A
  • Journal Title: Neurobiology of Aging Volume: 33 Issue: 5 Pages: 11-23
  • DOI: 10.1016/j.neurobiolaging.2011.10.028
  • NAID: 120003988394
  • Peer Reviewed
• [Journal Article] Exercise Is More Effective than Diet Control in Preventing High Fat Diet-induced β-Amyloid Deposition and Memory Deficit in Amyloid Precursor Protein Transgenic Mice. (2012)
  • Author(s): Maesako M
  • Journal Title: J Biol Chem. Volume: 287 Issue: 27 Pages: 23024-23033
  • DOI: 10.1074/jbc.m112.367011
  • Peer Reviewed
• [Journal Article] Environmental enrichment ameliorated high-fat diet-induced Aβ deposition and memory deficit in APP transgenic mice. (2012)
  • Author(s): Maesako M, Uemura K, Kubota M, Kuzuya A, Sasaki K, Asada M, Watanabe K, Hayashida N, Ihara M, Ito H, Shimohama S, Kihara T, Kinoshita A.
  • Journal Title: Neurobiol Aging Volume: 33
  • NAID: 120003988394
• [Journal Article] Gain of function by phosphorylation in Presenilin 1-mediated regulation of insulin signaling (2012)
  • Author(s): Maesako M, Uemura K, Kuzuya A, Sasaki K, Asada M, Watanabe K, Ando K, Kubota M, Akiyama H, Takahashi R, Kihara T, Shimohama S, Kinoshita A.
  • Journal Title: J Neurochem Volume: 121 Issue: 6 Pages: 964-973
  • DOI: 10.1111/j.1471-4159.2012.07741.x
  • Peer Reviewed
• [Journal Article] N-cadherin enhances APP dimerization at the extracellular domain and modulates Aβproduction (2011)
  • Author(s): Asada-Utsugi M, Uemura K, Noda Y, Kuzuya A, Maesako M, Ando K, Kubota M, Watanabe K, Takahashi M, Kihara T, Shimohama S, Takahashi R, Berezovska O, Kinoshita A
  • Journal Title: J Neurochem Volume: 119(2) Pages: 354-63
• [Journal Article] N-cadherin enhances APP dimerization at the extracellular domain and modulates Aβ production. (2011)
  • Author(s): Asada-Utsugi M, Uemura K, Noda Y, Kuzuya A, Maesako M, Ando K, Kubota M, Watanabe K, Takahashi M, Kihara T, Shimohama S, Takahashi R, Berezovska O, Kinoshita A.
  • Journal Title: J Neurochem. Volume: 119 Pages: 354-63
• [Journal Article] Presenilin regulates insulin signaling via a gamma-secretase-independent mechanism. (2011)
  • Author(s): Maesako M, Uemura K, Kuzuya A, Sasaki K, Asada M, Watanabe K, Ando K, Kubota M, Kihara T, Kinoshita A.
  • Journal Title: J Biol Chem. Volume: 286 Pages: 25309-16
• [Presentation] 銅はAPPダイマー化を促進し、アミロイド産生に影響する (2012)
  • Author(s): 植村健吾他
  • Organizer: 日本臨床神経学会
  • Place of Presentation: (ポスター発表)
• [Presentation] N-カドヘリンはAPPの細胞外ドメインダイマー化を促進し、Abeta産生を促進する (2011)
  • Author(s): 浅田めぐみ、植村健吾、木下彩栄他
  • Organizer: 神経科学会
  • Place of Presentation: (ポスター発表)
• [Remarks] 京都大学医学研究科・臨床神経学
  • URL: http://www.kuhp.kyoto-u.ac.jp/~neurology/
• [Remarks] 京都大学医学研究科人間健康科学系・在宅医療看護学分野
  • URL: http://kinoshita-lab.hs.med.kyoto-u.ac.jp/index.html