The functional role of Eph/ephrin signal as neuron-glia communication in the regulation of brain Abeta level

• Project/Area Number: 26893042
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: Hori Yukiko 東京大学, 薬学研究科(研究院), 助教 (80610683)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脳神経疾患 / 神経科学 / アルツハイマー病

Outline of Final Research Achievements

Amyloid-β peptide (Aβ) is linked to the pathogenesis of Alzheimer disease (AD). Therefore, it is important to reveal the mechanistic insights underlying regulation of brain Aβ level. In this research, we examined the functional role of EphA4/ephrin signal as neuron-glia communication in the regulation of brain Aβ level. We found that EphA4/ephrin signal modulates the Aβ level by altering the protein level of BACE, which is a limiting enzyme for Aβ　production.

Research Products

• [Journal Article] Role of apolipoprotein E in β-amyloidgenesis: isoform-specific effects on protofibril to fibril conversion of Aβ in vitro and brain Aβ deposition in vivo. (2015)
  • Author(s): Yukiko Hori, Tadafumi Hashimoto, Hidetoshi Nomoto, Bradley T Hyman, Takeshi Iwatsubo
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 24 Pages: 15163-15174
  • DOI: 10.1074/jbc.m114.622209
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease. (2015)
  • Author(s): Hori Y, Takeda S, Cho H, Wegmann S, Shoup TM, Takahashi K, Irimia D, Elmaleh DR, Hyman BT, Hudry E.
  • Journal Title: The Journal of Biological Chemistry Volume: 290 Issue: 4 Pages: 1966-1978
  • DOI: 10.1074/jbc.m114.586602
  • Peer Reviewed / Open Access
• [Presentation] EphA4を介したアルツハイマー病原因物質Aβ産生量制御機構の解明 (2015)
  • Author(s): 田村 謙典、堀 由起子、富田 泰輔
  • Organizer: 第14回 次世代を担う若手ファーマ・バイオフォーラム 2015
  • Place of Presentation: 千葉大学亥鼻キャンパス 医薬系総合研究棟（千葉）
  • Year and Date: 2015-09-12
• [Presentation] FDA APPROVED ASTHMA THERAPEUTIC AGENT IMPACTS AMYLOID BETA IN THE BRAIN IN A TRANSGENIC MODEL OF AD (2015)
  • Author(s): Y. Hori, D.R. Elmaleh, T.M. Shoup, K. Takahashi, S. Takeda, H. Cho, D. Irimia, B.T. Hyman, E. Hudry.
  • Organizer: The 12th international conference on Alzheimer’s & Parkinson’s diseases
  • Place of Presentation: Nice (France)
  • Year and Date: 2015-03-18 – 2015-03-22
• [Remarks] 東京大学大学院薬学系研究科 機能病態学教室
  • URL: http://www.f.u-tokyo.ac.jp/~neuropsc/