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

• 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• 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 / アルツハイマー病 / NMDA受容体 / DM232 / memantine / 認知機能調節 / グリシン結合部位

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
• [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, 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, 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, causes hippocampal dysfunction in mice (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, Isao Kitajima
  • Journal Title: Hippocampus 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, Kohji Fukunaga
  • Journal Title: Mol.Cell.Neurosci. Volume: 46 Pages: 101-107
  • Peer Reviewed
• [Journal Article] Essential role of meuron-enriched diacylglycerol kinase (DGK), DGKβ in neurite spine formation, contributing to cognitive function. (2010)
  • Author(s): Yasuhito Shirai, Takeshi Kouzuki, Kenichi Kakefuda, Shigeki Moriguchi, Atsushi Oyagi, Kyoji Horie, Shin-ya Morita, Masamitsu Shimazawa, Kohji Fukunaga, Junji Kakeda, Naoaki Saito, Hideaki Hara
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] A novel cognitive enhancer, spino[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one (ZSET1446/ST101), promotes hippocampal neurogenesis and ameliorates depressive behavior in olfactory bulbectomized mice. (2010)
  • Author(s): Norifumu Shioda, Yui Yamamoto, Feng Han, Shigeki Moriguchi, Yoshimasa Yamaguchi, Masataka Hino, Kohji Fukunaga
  • Journal Title: J.Pharmacol.Exp.Ther. Volume: 333 Pages: 43-50
  • Peer Reviewed
• [Journal Article] Platelet-activating factor-induced synaptic facilitation is associated with increased calcium/calmodulin-dependent protein kinase II, protein kinase C and extracellular signal-regulated kinase in the rat hippocampal CA1 region. (2010)
  • Author(s): Shigeki Moriquchi, Norifumi Shioda, Yui Yamamoto, Kohji Fukunaga
  • Journal Title: Neuroscience Volume: 166 Pages: 1158-1166
  • Peer Reviewed
• [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] 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] 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 (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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] 新生児期腹側海馬損傷ラットの前頭前皮質と海馬における興奮性神経伝達機能低下と統合失調症様行動評価 (2010)
  • Author(s): 矢吹悌、森口茂樹、中川西修、小野木弘志、只野武、福永浩司
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] Na+/Ca2+交換体(NCX)欠損マウスにおけるカルシウム/カルモデュリン依存性プロテインキナーゼIIの機能低下と認知機能障害 (2010)
  • Author(s): 森口茂樹、喜多紗斗美、岩本隆宏、福永浩司
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] 新生児期腹側海馬損傷ラット前頭前皮質と海馬におけるCaMKIIの機能低下 (2010)
  • Author(s): 矢吹悌、森口茂樹、中川西修、小野木弘志、只野武、福永浩司
  • Organizer: 第14回活性アミンに関するワークショップ
  • Place of Presentation: 仙台
  • Year and Date: 2010-08-27
• [Presentation] Memantine ameliorates the impairment of hippocampal long-term potentiation in olfactory bulbectomized mice. (2010)
  • Author(s): Shigeki Moriguchi, Yui Yamamoto, Norifumi Shioda, Kohji Fukunaga
  • Organizer: International Conference on Alzheimer's Disease
  • Place of Presentation: ホノルル、USA
• [Presentation] A novel cognitive enhancer, Spino[Imidazo[1,2-A]Pyridine-3,2-Indan]-2(3H)-One (ZSET1446), promotes hippocampal neurogenesis and ameliorates depressive behavior in olfactory bulbectomized mice. (2010)
  • Author(s): Kohji Fukunaga, Yui Yamamoto, Shigeki Moriguchi, Norifumi Shioda
  • Organizer: International Conference on Alzheimer's Disease
  • Place of Presentation: ホノルル、USA
• [Presentation] Impairment of cognitive function via decreased calcium/cakmodulin-dependent protein kinase II activity in Na+/Ca2+ exchanger type-2 deficit mice (2010)
  • Author(s): Shigeki Moriguchi, Satomi Kita, Takahiro Iwamoto, Kohji Fukunaga
  • Organizer: 包括型脳科学研究推進支援ネットワーク 夏のワークショップ
  • Place of Presentation: 札幌
• [Presentation] メタンフェタミン誘発行動逆耐性の機能不全にはCaMキナーゼII量活性異常が関与する (2010)
  • Author(s): 森口茂樹、竹島浩、福永浩司
  • Organizer: 第53回日本神経化学会
  • Place of Presentation: 神戸
• [Presentation] NCX3欠損マウスにおける自発運動量の亢進と細胞内カルシウム恒常性の異常 (2010)
  • Author(s): 森口茂樹、喜多紗斗美、岩本隆宏、福永浩司
  • Organizer: 第40回日本神経精神薬理学会
  • Place of Presentation: 仙台
• [Presentation] Abnormal behaviors of methamphetamine-induced sensitization is associated with impaired CaM kinase II activity in neural junctophilin deficient mice. (2010)
  • Author(s): Shigeki Moriguchi, Hiroshi Takeshima, Kohji Fukunaga
  • Organizer: 平成22年度シナプス研究会「記憶学習行動の基盤としてのシナプス可塑性」
  • Place of Presentation: 名古屋