Role of tissue-type plasminogen activator and matrix metalloproteinase in dementia

• Project/Area Number: 23790289
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUZUKI Yasuhiro 浜松医科大学, 医学部, 助教 (00324343)
• Co-Investigator(Renkei-kenkyūsha): NAGAI Nobuo 長浜バイオ大学, アニマルバイオサイエンス学科, 教授 (90260281) ; YAMAKAWA Kasumi 浜松医科大学, 医学部附属病院, 薬剤師 (70563287)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 組織型プラスミノゲン活性化因子 / 血液脳関門透過性 / 組織型プラスミノーゲン活性化因子 / マトリックスメタロプロテアーゼ

Outline of Final Research Achievements

We studied on vascular dementia by using mice with deficient of tissue-type plasminogen activator (t-PA).　t-PA bound to a receptor of lipid metabolism, activated the endothelial cells, induced the vascular endothelial growth factor, changed the defense function of brain, induced and activated catabolic enzymes to cerebral cells by the synergistic action with reactive oxygen species induced by cell death. Endogenous t-PA may contribute to potential escape response and modulation of motivation in vascular dementia.

Research Products

• [Journal Article] Urokinase-type plasminogen activator and plasminogen mediate activation of macrophage phagocytosis during liver repair in vivo. (2012)
  • Author(s): Kawao N, Nagai N, Tamura Y, Horiuchi Y, Okumoto K, Okada K, Suzuki Y, Umemura K, Yano M, Ueshima S, Kaji H, Matsuo O.
  • Journal Title: Thromb Haemost Volume: 107 Issue: 04 Pages: 749-59
  • DOI: 10.1160/th11-08-0567
  • Peer Reviewed
• [Journal Article] Combination of Reactive Oxygen Species and Tissue-Type Plasminogen Activator Enhances the Induction of Gelatinase B in Brain Endothelial Cells (2012)
  • Author(s): Harada K, Suzuki Y, Yamakawa K, Kawakami J, Umemua K.
  • Journal Title: Int J Neurosci Volume: 122 Issue: 2 Pages: 53-59
  • DOI: 10.3109/00207454.2011.623808
  • Peer Reviewed
• [Presentation] マウス中大脳動脈閉塞後の血液脳関門の加圧凍結法による電子顕微鏡観察. (2015)
  • Author(s): 鈴木康裕、村中祥悟、外村和也、山川花朱美、永井信夫、梅村和夫
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] Tissue-type plasminogen activator modulates adrenergic nerve function after stroke (2013)
  • Author(s): 鈴木康裕
  • Organizer: 第86回日本薬理学会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 脳梗塞後の行動障害における内因性組織型プラスミノゲン活性化因子の役割 (2012)
  • Author(s): Yasuhiro Suzuki, Malgorzata Zajda, Nobuo Nagai, Kazuo Umemura
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 国立京都国際会館
• [Presentation] プラスミノゲン活性因子は虚血培養内皮細胞において血管内皮細胞増殖因子を誘導した。
  • Author(s): 鈴木康裕、永井信夫、山川花朱美、外村和也、梅村和夫
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 仙台国際センター