| Project/Area Number |
16590829
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology (2005)
Okayama University (2004) |
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Principal Investigator |
MATSUBARA Etsuro National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Chief, (研究所)・アルツハイマー病研究部, 室長 (70219468)
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| Co-Investigator(Kenkyū-buntansha) |
SHOJI Mikio Hirosaki University, Professor, 医学部, 教授 (60171021)
ABE Koji Okayama University, Graduate School of Medicine and Dentistry, Professor, 大学院・医歯薬学総合研究科, 教授 (20212540)
IKEDA Masaki Gunma University, Graduate School of Medicine, Instructor, 大学院・医学系研究科, 助手 (50222899)
ORIUCHI Noboru Gunma Univeristy, Graduate School of Medicine, Associated professor, 大学院・医学系研究科, 助教授 (40292586)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Alzheimer's disease / Aβ oligomer / ELISA / melatonin / clearance / Aβ / オリゴマー |
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| Research Abstract |
To assess whether melatonin is accelerating agent for Aβ clearance out of the brain, we investigated it in transgenic model mice for Alzheimer's disease (AD). It is relevant to note that melatonin has ability to upregulate Aβ clearance out of the brain, by driving the equilibrium not only from insoluble to soluble, but also from oligomeric to monomeric Aβ. Melatonin also corrected the spatial reference memory performance without reducing senile plaques burdens in the APP transgenic model. These finding suggests that the target-molecule for melatonin can be Aβ oligomer, supporting the previous repots showing that a soluble Aβ assembly rather than the accumulation of amyloid plaques is sufficient to disrupt memory.
Consequently, above mentioned data led us to develop the monoclonal antibody specific to Aβ oligomer for the therapeutic intervention for Alzheimer's disease. After the tetramer bands cutted off immunized onto mice pad, we successfully obtained several monoclones which specifically immunoprecipitate Aβ oligomers. It is important to note that they do not cross-react to full-length amyloid precursor protein (APP), carboxyl-terminal derivatives of APP, or soluble Aβ monomer obtained from AD brain. We also found that our antibodies appear to be against "neurotoxic epitopes" and/or "assemblying epitopes", which can be explored as therapeutic antibody for Alzheimer's disease.
We are sure that neurotoxic Aβ oligomer-targeted therapy should be one of the most promising intervention therapy for Alzheimer's disease. Among them, immunodepletion and/or immunoneutralization of toxic Aβ oligomer using our antibodies will provide the most specific treatment for Alzheimer's disease.
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