Analysis of prevention of Alzheimer's disease based on underlying pathology

• Project/Area Number: 26500006
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: Gifu University
• Principal Investigator: Nakagawa Toshiyuki 岐阜大学, 大学院医学系研究科, 教授 (00271502)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 小胞体ストレス / フラボノイド / 認知症 / 記憶 / 想起 / ケルセチン / 記憶再生 / ATF4 / アルツハイマー病 / 食品成分 / 介入試験 / GADD34 / アルツハイマーモデルマウス / 食生活

Outline of Final Research Achievements

Purpose of this study is to explore the action of quercetin and its target gene GADD34 for amyloid-beta production and impairment of learning and memory in Alzheimer’s disease (AD) model mice APP23. In addition, pilot study of intervention trial of quercetin high content onion to early stage AD patients was carried out. In this study, deterioration of memory impairment was delayed in AD mice feeding quercetin-containing food compared with AD mice feeding control food. The levels of GADD34 in the brains of AD mice feeding quercetin-containing food were higher than those of AD mice feeding control food. In addition, score of recall using HDS-R in early stage AD patients was significantly improved. These results suggest that quercetin may be promising functional food molecule to prevent memory impairment.

Research Products

• [Journal Article] Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients. (2016)
  • Author(s): Nakagawa T, Itoh M, Ohta K, Hayashi Y, Hayakawa M, Yamada Y, Akanabe H, Chikaishi T, Nakagawa K, Itoh Y, Muro T, Yanagida D, Nakabayashi R, Mori T, Saito K, Ohzawa K, Suzuki C, Li S, Ueda M, Wang MX, Nishida E, Islam S, Tana, Kobori M, Inuzuka T.
  • Journal Title: NeuroReport Volume: 27 Issue: 9 Pages: 671-676
  • DOI: 10.1097/wnr.0000000000000594
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Quercetin reduces eIF2α phosphorylation by GADD34 induction. (2015)
  • Author(s): Hayakawa M, Itoh M, Ohta K, Li S, Ueda M, Wang MX, Nishida E, Islam S, Suzuki C, Ohzawa K, Kobori M, Inuzuka T, Nakagawa T.
  • Journal Title: Neurobiology of Aging Volume: 36 Issue: 9 Pages: 2509-2518
  • DOI: 10.1016/j.neurobiolaging.2015.05.006
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] OCIAD2 activates γ-secretase to enhance amyloid β production by interacting with nicastrin. (2014)
  • Author(s): Han J, Jung S, Jang J, Kam TI, Choi H, Kim BJ, Nah J, Jo DG, Nakagawa T, Nishimura M, Jung YK.
  • Journal Title: Cellular and Molecular Life Sciences Volume: 未定 Issue: 13 Pages: 2561-2576
  • DOI: 10.1007/s00018-013-1515-x
  • Peer Reviewed
• [Presentation] 記憶の再生と小胞体ストレスシグナル (2016)
  • Author(s): 中川敏幸
  • Organizer: 第11回小胞体ストレス研究会
  • Place of Presentation: 岐阜大学サテライトキャンパス(岐阜市)
  • Year and Date: 2016-10-10
• [Presentation] Motor neurons were degenerated in the Prune homolog 2 (Drosophila) (Prune2) gene deficient mice generated by CRISPR/Cas9 system. (2015)
  • Author(s): Masanori Itoh, Emika Nishida, Saiful Islam, Shimo Li, Masatake Osawa, Dongsoo Lee, Huayue Chen , Masashi Ueda, Miao-xing Wang, Miki Hayakawa, Gen Ikeno, Koki Ichihashi, Kazuyuki Okamoto, Jun Tsutsumi, Toshiyuki Nakagawa
  • Organizer: 45th ANNUAL MEETING Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] 小胞体ストレス制御による記憶・認知機能改善作用 (2014)
  • Author(s): 中川敏幸
  • Organizer: 第12回日本機能性食品医用学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2014-12-13 – 2014-12-14
  • Invited
• [Presentation] 肥満・糖尿病によるアルツハイマー病モデルマウスの病態解明 (2014)
  • Author(s): 早川実希、伊藤正徳、太田和徳、李 詩沫、上田昌史、王 淼星、西田江美香、中川敏幸
  • Organizer: 第12回日本機能性食品医用学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2014-12-13 – 2014-12-14
• [Remarks] 岐阜大学大学院医学系研究科 神経生物分野
  • URL: http://www1.gifu-u.ac.jp/~neurobio/