Development of Alzheimer's disease therapeutics mediate for enhancement of synaptic transmission

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790509
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Tohoku University
• Principal Investigator: MORIGUCHI Shigeki 東北大学, 大学院・薬学研究科, 講師 (70374949)
• Project Period (FY): 2010 – 2011
• Keywords: sunifiram / LTP / CaMキナーゼII / NMDA受容体グリシン結合部位 / OBXマウス / 電気生理学 / PKC / 認知機能

Research Abstract

Sunifiram is a new pyrrolidone nootropic drug structurally related to piracetam, being development for neurodegenerative disorder like Alzheimer's disease. Sunifiram modulates glycine binding site of NMDAR concomitant increased PKC・activity through Src family kinase. Enhancement of PKC・activity triggered to potentiates hippocampal LTP through activation of CaMKII.

Research Products

• [Journal Article] Heparin-binding EGF-like growth factor is required for synaptic plasticity and memory formation (2011)
  • Author(s): Atsushi Oyagi, Shigeki Moriguchi, Atsumi Nitta, Kenta Murata, Yasuhisa Oida, Kazuhiro Tsuruma, Masamitsu Shimazawa, Kohji Fukunaga and Hideaki Hara
  • Journal Title: Brain Res Volume: 1419 Pages: 97-104
  • Peer Reviewed
• [Journal Article] Pharmacological study on Alzheimer's drugs targeting for calcium/calmodulin-dependent protein kinase II (2011)
  • Author(s): Shigeki Moriguchi
  • Journal Title: J. Pharmacol. Sci Volume: 117 Pages: 6-11
  • Peer Reviewed
• [Journal Article] Sigma-1 receptor stimulation by dehydroepiandrosterone ameliorates cognitive impairment through activation of CaM kinase II, protein kinase C and extracellular signal-regulated kinase in olfactory bulbectomized mice (2011)
  • Author(s): Shigeki Moriguchi, Yui Yamamoto, Tatsuya Ikuno and Kohji Fukunaga
  • Journal Title: J. Neurochem Volume: 117 Pages: 879-891
  • Peer Reviewed
• [Journal Article] Prandial increases of leptin and orexin in the brain modulate spatial learning and memory (2011)
  • Author(s): Yutaka Oomura, Shuji Aou, Kohji Fukunaga, Shigeki Moriguchi and Kazuo Sasaki
  • Journal Title: Neurosci. Behav. Physiol Volume: 41 Pages: 233-242
  • Peer Reviewed
• [Journal Article] Reduced expression of the ATRX gene, a chromatin-remodeling factor (2011)
  • Author(s): Tatsuya Nogami, Hideyuki Beppu, Takashi Tokoro, Shigeki Moriguchi, Norifumi Shioda, Kohji Fukunaga, Toshihisa Ohtsuka, Yoko Ishii, Masakiyo Sasahara, Yutaka Shimada, Hisao Nishijo, En Li and Isao Kitajima
  • Journal Title: causes hippocampal dysfunction in mice Volume: 21 Pages: 678-687
  • Peer Reviewed
• [Journal Article] Ca^<2+>/calmodulin-dependent protein kinase II and protein kinase C activities mediate extracellular glucose-regulated hippocampal synaptic efficacy (2011)
  • Author(s): Shigeki Moriguchi, Yutaka Oomura, Norifumi Shioda, Feng Han, Nobuaki Hori, Shuji Aou and Kohji Fukunaga
  • Journal Title: Mol. Cell. Neurosci Volume: 46 Pages: 101-107
  • Peer Reviewed
• [Presentation] Stimulation of sigma-1 receptor improves cognitive functions through CaMKII activation (2011)
  • Author(s): Kohji Fukunaga, Shigeki Moriguchi, Yui Yamamoto, Norifumi Shioda
  • Organizer: 40th. Society for Neuroscience ; Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20111112-16
• [Presentation] Characterization of novel Alzheimer's therapeutic, ST101 in brain functions (2011)
  • Author(s): Yui Yamamoto, Norifumi Shioda, Shigeki Moriguchi, Kohji Fukunaga
  • Organizer: 40th. Society for Neuroscience ; Annual Meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20111112-16
• [Presentation] MPTP処置パーキンソン病モデルマウスにおける認知機能障害とCaMキナーゼII活性低下の関連性 (2011)
  • Author(s): 森口茂樹、矢吹悌、福永浩司
  • Organizer: 第41回日本神経精神薬理学会
  • Place of Presentation: 東京
  • Year and Date: 20111027-29
• [Presentation] 嗅球摘出マウスにおけるシグマ1受容体活性化による認知機能障害の改善 (2011)
  • Author(s): 森口茂樹、山本由似、福永浩司
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 金沢
  • Year and Date: 20110926-28
• [Presentation] DHEAによるsigma1受容体刺激はCaMKII、PKCおよびERKの活性化を介して嗅球摘出マウスにおける認知機能障害を改善する (2011)
  • Author(s): 森口茂樹、山本由似、福永浩司
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 20110914-17
• [Presentation] Sigma1受容体を介した認知機能調節 (2011)
  • Author(s): 森口茂樹、山本由似、福永浩司
  • Organizer: 第13回応用薬理シンポジウム
  • Place of Presentation: 船橋
  • Year and Date: 20110903-04
• [Presentation] 新生仔期腹側海馬(NVH)損傷ラットにおけるCaMKII 活性低下と認知機能障害 (2011)
  • Author(s): 矢吹悌、森口茂樹、塩田倫史、中川西修、小野木弘志、丹野孝一、只野武、福永浩司
  • Organizer: 第13回ブレインサイエンス研究会
  • Place of Presentation: 熊本
  • Year and Date: 20110528-29
• [Presentation] 矢吹悌、森口茂樹、塩田倫史、中川西修、小野木弘志、丹野孝一、只野武、福永浩司 (2011)
  • Author(s): 新生仔期腹側海馬(NVH)損傷ラットにおける認知機能障害とCaMKII 活性低下の関連性
  • Organizer: 第50回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2011-10-30
• [Presentation] 新規認知機能改善薬sunifiram の作用機序に関する研究 (2011)
  • Author(s): 田中智哉、森口茂樹、福永浩司
  • Organizer: 第50回日本薬学会東北支部大会
  • Place of Presentation: 仙台
  • Year and Date: 2011-10-30
• [Presentation] 神経変性疾患モデルマウスを用いたカルシウム恒常性の制御と認知機能調節 (2011)
  • Author(s): 森口茂樹
  • Organizer: 平成23年度日本薬学会東北支部学術講演会
  • Place of Presentation: 仙台
  • Year and Date: 2011-07-16