Drug development targeting for regeneration of neurovascular units in neurodegenerative disorders
Project/Area Number |
22390109
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied pharmacology
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Research Institution | Tohoku University |
Principal Investigator |
FUKUNAGA Kohji 東北大学, 大学院・薬学研究科, 教授 (90136721)
|
Co-Investigator(Kenkyū-buntansha) |
IWABUCHI Yoshiharu 東北大学, 大学院・薬学研究科, 教授 (20211766)
ITO Yoshihisa 日本大学, 薬学部, 教授 (50151551)
MORIGUCHI Shigaki 東北大学, 大学院・薬学研究科, 講師 (70374949)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2012: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2010: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
|
Keywords | 薬物治療学 / ST101 / T型カルシウムチャネル / アルツハイマー病治療薬 / アミロイド前駆タンパク質 / 神経血管ユニット / 神経変性疾患 / 血管再生 / 神経再生 / CaMKII / バナジウム有機錯体 / 心肥大 / ジストロフィン / eNOS / カルモデュリン |
Research Abstract |
ST101 stimulates memory molecule, Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the hippocampus. In the present study, we investigated whether chronic administration of the neurovascular regenerative compound, ST101 elicits long lasting ameliorating effects on brain functions and defined the molecular mechanism underlying their therapeutic effects in the neurodegenerative disorders. ST101 was now under investigation in Phase II clinical trial of U.S.A. We defined T type voltage-gated calcium channel as molecular target of ST101. We next introduced novel and potent derivative, SAK3 by using neuro2A cells overexpressing T type voltage-gated calcium channel. This is the first discovery of activators of T type voltage-gated calcium channel in the world. The most promising evidence in our studies is that T type calcium channel is novel therapeutic target of Alzheimer therapy to restore the neural networks in the neurodegenerative disorders.
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Report
(4 results)
Research Products
(230 results)
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[Journal Article] Influence of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on socioemotional behaviors in offspring rats.2013
Author(s)
Nguyen AT, Nishijo M, Hori E, Nguyen NM, Pham TT, Fukunaga K, Nakagawa H, Tran AH, Nishijo H.
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Journal Title
Environ Health Insights
Volume: 7
Pages: 1-14
DOI
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Peer Reviewed
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[Journal Article] The Disturbance of Hippocampal CaMKII/PKA/PKC Phosphorylation in Early Experimental Diabetes Mellitus.2013
Author(s)
Liao MH, Xiang YC, Huang JY, Tao RR, Tian Y, Ye WF, Zhang GS, Lu YM, Ahmed MM, Liu ZR, Fukunaga K, Han F.
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Journal Title
CNS Neurosci Ther.
Volume: -
Issue: 5
Pages: 329-36
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[Journal Article] The γ-secretase blocker DAPT reduces the permeability of the blood-brain barrier by decreasing the ubiquitination and degradation of occludin during permanent brain ischemia.2013
Author(s)
Zhang GS, Tian Y, Huang JY, Tao RR, Liao MH, Lu YM, Ye WF, Wang R, Fukunaga K, Lou YJ, Han F.
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Journal Title
CNS Neurosci Ther.
Volume: 19(1)
Issue: 1
Pages: 53-60
DOI
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Peer Reviewed
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[Journal Article] Tao RR, Huang JY, Shao XJ, Ye WF, Tian Y, Liao MH, Fukunaga K, Lou YJ, Han F, Lu YM. Ischemic injury promotes Keap1 nitration and disturbance of antioxidative responses in endothelial cells: a potential vasoprotective effect of melatonin.2013
Author(s)
Tao RR, Huang JY, Shao XJ, Ye WF, Tian Y, Liao MH, Fukunaga K, Lou YJ, Han F, Lu YM.
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Journal Title
J Pineal Res.
Volume: 54(3)
Issue: 3
Pages: 271-281
DOI
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Peer Reviewed
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[Journal Article] Reduced expression of the ATRX gene, a chromatin-remodeling factor, causes hippocampal dysfunction in mice2011
Author(s)
Nogami T, Beppu H, Tokoro T, Moriguchi S, Shioda N, Fukunaga K, Ohtsuka T, Ishii Y, Sasahara M, Shimada Y, Nishijo H, Li E, Kitajima I
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Journal Title
Hippocampus
Volume: 21
Pages: 678-687
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Peer Reviewed
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[Journal Article] Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons2010
Author(s)
Sanda M, Ohara N, Kamata A, Hara Y, Tamaki H, Sukegawa J, Yanagisawa T, Fukunaga K, Kondo H, Sakagami H
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Journal Title
Neurosci. Res
Volume: 67
Pages: 126-136
Related Report
Peer Reviewed
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[Journal Article] Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice2010
Author(s)
Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K, Yamasaki N, Toyama K, Adachi M, Umeda M, Araki T, Fukunaga K, Kondo H, Sakagami H, Miyakawa T
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[Journal Article] Essential role of neuron-enriched diacylglycerol kinase (DGK), DGKbeta in neurite spine formation, contributing to cognitive function2010
Author(s)
Shirai Y, Kouzuki T, Kakefuda K, Moriguchi S, Oyagi A, Horie K, Morita SY, Shimazawa M, Fukunaga K, Takeda J, Saito N, Hara H
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Related Report
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[Journal Article] Reduced expression of the ATRX gene, a chromatin-remodeling factor causes hippocampal dysfunction in mice.2010
Author(s)
Nogami T, Beppu H, Tokoro T, Moriguchi S, Shioda N, Fukunaga K, Ohtsuka T, Ishii Y, Sasahara M, Shimada Y, Nishijo H, Li E, Kitajima I
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Journal Title
Hippocampus.
Volume: (未定)(印刷中)
Related Report
Peer Reviewed
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[Journal Article] Essential role of neuron-enriched diacylglycerol kinase (DGK), DGKb eta in neurite spine formation, contributing to cognitive function.2010
Author(s)
Shirai Y, Kouzuki T, Kakefuda K, Moriguchi S, Oyagi A, Horie K, Morita SY, Shimazawa M, Fukunaga K, Takeda J, Saito N, Hara H
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Related Report
Peer Reviewed
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[Journal Article] Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice.2010
Author(s)
Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K, Yamasaki N, Toyama K, Adachi M, Umeda M, Araki T, Fukunaga K, Kondo H, Sakagami H, Miyakawa T
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons.2010
Author(s)
Sanda M, Ohara N, Kamata A, Hara Y, Tamaki H, Sukegawa J, Yanagisawa T, Fukunaga K, Kondo H, Sakagami H
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Journal Title
Neurosci.Res.
Volume: 67
Pages: 126-136
Related Report
Peer Reviewed
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