ovel cerebroprotectants targeting ER stress or hypoxia inducible factor

• Project/Area Number: 19591012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokai University
• Principal Investigator: TAKIZAWA Shunya Tokai University, 医学部, 教授 (70197234)
• Co-Investigator(Kenkyū-buntansha): MIYATA Toshio 東北大学, 医学部, 教授 (10222332)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経病態薬理学 / advanced glycation end product / hypoxia inducible factor / 脳梗塞 / 小胞体ストレス / フリーラジカル

Research Abstract

AGE形成抑制作用をもつ新規化合物TM2002は小胞体ストレス・AGE形成・フリーラジカル産生を抑制しラット脳梗塞巣の縮小効果を認めた。HIF活性を高める新規化合物TM6008は、glut-3増加作用を介して海馬の遅延型神経細胞死を回避し、apoptosisを抑制した。TM6008は低酸素環境負荷後の培養細胞において、HIFの発現を活性化・持続させ、VEGFなどHIF下流因子群を発現させた。

Research Products

• [Journal Article] Advanced glycation end products in patients with cerebral infarction (2009)
  • Author(s): Ohnuki Y, Nagano R, Takizawa S, Takagi S, Miyata S.
  • Journal Title: Intern Med (in press)
  • NAID: 130000108031
  • Peer Reviewed
• [Journal Article] Advanced glycatjon end products in patients with cerebral infarction. (2009)
  • Author(s): Ohnuki Y
  • Journal Title: Intern Med (In press)
  • Peer Reviewed
• [Journal Article] A novel class of inhibitor of advanced glycation end products ameliorates renal and cardiovascular damage in experimental rat models (2008)
  • Author(s): Izuhara Y, Nangaku M, Takizawa S, Takahashi S, Shao J, Oishi H, Kobayashi H, Charles van Ypersele de Strihou, Miyata T.
  • Journal Title: Nephrol. Dial. Transpl 23 Pages: 497-509
  • Peer Reviewed
• [Journal Article] A novel class of inhibitor of advanced glycation end products ameliorates renal and cardiovascular damage in experimental rat models (2008)
  • Author(s): Izuhara Y
  • Journal Title: Nephrol. Dial. Transpl 23 Pages: 497-509
  • Peer Reviewed
• [Journal Article] A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia (2007)
  • Author(s): Nangaku M, Izuhara Y, Takizawa S, Yamashita T, Ohneda O, Yamamoto M, van Ypersele de Strihou C, Hirayama N, Miyata T
  • Journal Title: Arterioscler Thromb Vasc Biol. 27 Pages: 2548-2554
  • Peer Reviewed
• [Journal Article] A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia (2007)
  • Author(s): Takizawa S, Izuhara Y, Kitao Y, HoriO, Ogawa S, Morita Y, Takagi S, Kurokawa K, van Ypersele de Strihou C, Miyata T
  • Journal Title: Brain Res 1183 Pages: 124-137
  • Peer Reviewed
• [Journal Article] A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia (2007)
  • Author(s): Takizawa S
  • Journal Title: Brain Res 1183 Pages: 124-137
  • Peer Reviewed
• [Journal Article] A novel class of prolyl hydroxylase inhibitors induces angiogenesis and exerts organ protection against ischemia (2007)
  • Author(s): Nangaku M
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 2548-2554
  • Peer Reviewed
• [Presentation] A novel sartan derivative with very low angiotensin II type 1 receptor affinity reduces infarct volume in rat focal cerebral ischemia (2008)
  • Author(s): Takizawa S, Izuhara Y, Uesugi T, Nagata E, Takagi S, Miyata T
  • Organizer: The 4th Korean-Japan Stroke Conference
  • Place of Presentation: Fukuoka
• [Presentation] 新規prolyl hydroxylase 阻害薬が神経細胞系培養細胞においてHIF下流因子に与える影響 (2008)
  • Author(s): 紺谷智、永田栄一郎、瀧澤俊也、高木繁治
  • Organizer: 第20回日本脳循環代謝学会総会
  • Place of Presentation: 東京
• [Presentation] 新規prolyl hydroxylase 阻害薬がHIF下流因子に与える影響 (2008)
  • Author(s): 紺谷智、永田栄一郎、清水美衣、瀧澤俊也、高木繁治、宮田敏男
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
• [Presentation] A novel sartan derivative with very low angiotensin II type I receptor affinity reduces infarct volume in rat Focal cerebral ischemia (2008)
  • Author(s): Takizawa S
  • Organizer: The 4^<th> Korean-Japan stroke Conference
  • Place of Presentation: Fukuoka
• [Presentation] Advanced glycation end products in patients with cerebral infarction (2007)
  • Author(s): Takizawa S, Morita Y, Nagano R, Izuhara Y, Takagi S, Miyata T
  • Organizer: The 2nd Meeting of Asian Stroke Forum
  • Place of Presentation: Kyoto
• [Presentation] inhibiting degradation of hypoxiainducible factor increases neural stem cells in mouse focal ischemia (2007)
  • Author(s): Uesugi T, Takizawa S, Izuhara Y, Morita Y, Takagi S, Miyata T
  • Organizer: XXIIInd International Symposium on Cerebral Blood Flow, Metabolism, and Function
  • Place of Presentation: Osaka
• [Presentation] A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat transient focal ischemia (2007)
  • Author(s): Takizawa S, Izuhara Y, Morita Y, Uesugi T, Takagi S, Miyata T
  • Organizer: XXIIInd International Symposium on Cerebral Blood Flow, Metabolism, and Function
  • Place of Presentation: Osaka
• [Presentation] マウス中大脳動脈永久閉塞モデルでの虚血誘導因子の脳保護効果の検討 (2007)
  • Author(s): 植杉剛, 森田優子, 瀧澤俊也, 高木繁治, 宮田敏男
  • Organizer: 第48回日本神経学会総会
  • Place of Presentation: 名古屋