Regulation of brian amyloid deposition by angiotensin receptor type Ia

• Project/Area Number: 26430057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Iwate Medical University
• Principal Investigator: ZOU KUN 岩手医科大学, 薬学部, 講師 (40450837)
• Co-Investigator(Renkei-kenkyūsha): KOMANO HIROTO 岩手医科大学, 薬学部, 教授 (40170378)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アルツハイマー病 / 高血圧症 / アンギオテンシン受容体 / アミロイド / アミロイド沈着 / アミロイドベータ蛋白

Outline of Final Research Achievements

Alzheimer's disease (AD)is characterized by neuronal loss and cerebral accumulation of amyloid-β protein (Aβ) and lowering the generation of Aβ is a pivotal approach in the strategy of Alzheimer's disease treatment. Midlife hypertension is a major risk factor for the future onset of sporadic AD and the use of some antihypertensive drugs may decrease the incidence of AD. However, it is largely unknown how the blood pressure regulation system is associated with the pathogenesis of AD. Here we found that the deficiency of angiotensin type 1a receptor (AT1a), a key receptor for regulating blood pressure, significantly decreased Aβ generation and amyloid plaque formation in a mouse model of AD. Our results suggest that removal of life style factors or stresses that stimulate AT1a to elevate blood pressure may decrease Aβ generation and brain amyloid accumulation, thereby preventing the pathogenesis of AD.

Research Products

• [Journal Article] Regulation of Aβ production by angiotensin receptor type Ia (2016)
  • Author(s): Kun Zou
  • Journal Title: Seikagaku Volume: 88 Pages: 771-775
  • NAID: 40021054398
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Angiotensin type 1a receptor deficiency decreases amyloid β-protein generation and ameliorates brain amyloid pathology. (2015)
  • Author(s): Liu J, Liu S, Matsumoto Y, Murakami S, Sugakawa Y, Kami A, Tanabe C, Maeda T, Michikawa M, Komano H, Zou K.
  • Journal Title: Sci Rep. Volume: 5 Issue: 1 Pages: 12059-12059
  • DOI: 10.1038/srep12059
  • Peer Reviewed / Open Access
• [Journal Article] Conversion of Aβ43 to Aβ40 by the successive action of angiotensin-converting enzyme 2 and angiotensin-converting enzyme. (2014)
  • Author(s): Shuyu Liu, Junjun Liu, Yukie Miura, Chiaki Tanabe, Tomoji Maeda, Yasuo Terayama, Anthony J. Turner, Kun Zou, Hiroto Komano
  • Journal Title: J Neurosci Res. Volume: 92 Issue: 9 Pages: 1178-1186
  • DOI: 10.1002/jnr.23404
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] ACE deficiency increases amyloid plaque burden in APP transgenic mouse brain (2016)
  • Author(s): 鄒鶤、劉しゅ余、劉俊俊、松元葵、沈雪峰、横森未来、下方浩史、道川誠、駒野宏人
  • Organizer: 第35回日本認知症学会学術集会 東京 2016年12月1日
  • Place of Presentation: 東京都
  • Year and Date: 2016-12-01
• [Presentation] アンギオテンシン受容体によるアミロイドβ蛋白産生制御 (2015)
  • Author(s): 駒野宏人、鄒鶤
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学大会合同大会ワークショップ
  • Place of Presentation: 神戸市
  • Year and Date: 2015-12-02
  • Invited
• [Presentation] レニン・アンギオテンシン系とAβ除去 (2015)
  • Author(s): 鄒鶤、駒野宏人
  • Organizer: 第34回日本認知症学会学術集会 シンポジウム
  • Place of Presentation: 青森市
  • Year and Date: 2015-10-04
  • Invited
• [Presentation] Angiotensin type 1a receptor deficiency ameliorates brain amyloid pathology by regulating γ-secretase complex formation (2015)
  • Author(s): Junjun Liu, Shuyu Liu, Yukino Matsumoto, Saki Murakami, Yusuke Sugakawa, Ayako Kami, Chiaki Tanabe, Tomoji Maeda, Makoto Michikawa, Hiroto Komano, Kun Zou
  • Organizer: 第54回 日本薬学会東北支部大会
  • Place of Presentation: 矢巾町
  • Year and Date: 2015-09-26
• [Presentation] Differential effects of angiotensin II receptor blockers on Aβ generation (2015)
  • Author(s): 劉俊俊、劉しゅう余、村上 咲、菅川 悠介、賀美 綾子、田邊 千晶、前田智司、鄒鶤、駒野宏人
  • Organizer: 第58回日本神経化学会大会
  • Place of Presentation: 大宮市
  • Year and Date: 2015-09-13
• [Presentation] Angiotensin type 1a receptor deficiency decreases amyloid β-protein production and ameliorates brain amyloid pathology (2015)
  • Author(s): Kun Zou, Junjun Liu, Shuyu Liu, Yukino Matsumoto, Saki Murakami, Yusuke Sugakawa, Ayako Kami, Chiaki Tanabe, Tomoji Maeda, Makoto Michikawa, Hiroto Komano
  • Organizer: 25th Meeting of The International Society For Neurochemistry
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2015-08-27
  • Int'l Joint Research
• [Presentation] Conversion of Aβ43 to Aβ40 by the successive action of angiotensin-converting enzyme-2 and angiotensin-converting enzyme. (2014)
  • Author(s): Shuyu Liu, Kun Zou, Junjun Liu, Yu Fujita, Tomoji Maeda, Yasuo Terayama, Anthony J. Turner, Hiroto Komano
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Angiotensin type 1a receptor deficiency attenuates amyloid beta-protein production and ameliorates brain amyloid pathology. (2014)
  • Author(s): Kun Zou, Junjun Liu, Shuyu Liu, Yukino Matsumoto, Saki Murakami, Chiaki Tanabe, Tomoji Maeda, Makoto Michikawa, Hiroto Komano
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] アンギオテンシン受容体による脳内アミロイド蓄積制御機構の解明. (2014)
  • Author(s): Kun Zou, Junjun Liu, Shuyu Liu, Yukino Matsumoto, Saki Murakami, Chiaki Tanabe, Tomoji Maeda, Makoto Michikawa, Hiroto Komano
  • Organizer: 第57回日本神経化学会大会
  • Place of Presentation: 奈良市
  • Year and Date: 2014-09-29 – 2014-10-01