2007 Fiscal Year Final Research Report Summary
Progress from the endogenous protective factor against Alzheimer's disease
| Project/Area Number |
18590240
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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 |
General pharmacology
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| Research Institution | Keio University |
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Principal Investigator |
TERASHITA Kenzo Keio University, School of Medicine, Assistant Professor (00163915)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Masaaki Keio University, School of Medicine, Associate Professor (70222297)
CHIBA Ibmohiro Keio University, School of Medicine, Instructor (60398617)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Alzheimer's disease / Neuronal death / Colivelin / Brain atrooh / Humanin |
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| Research Abstract |
Development of effective Alzheimer's disease (AD) therapy is urgently required because AD currently affects nearly 2.5% of the population in industrialized countries. We have identified a novel neuroprotective peptide named humanin (HN) from an occipital lobe of an AD patient. Very recently, we also identified a novel cell-surface receptor for UN (HNR), which belongs to the IL-6 receptor family and is consisting of three subunits, WSX-1, CNTFRalpha, and gp 130. Analysis of the physiological function of HNR may lead to the development of an effective therapy for AD because the biological effect evoked by HN/HNR is likely to regulate the pathogenesis of AD.
In this study, we performed i) analysis of the function of HNR, ii) development of a novel AD model with severe brain atrophy, iii) identification of HN/UN-like molecules, and iv) analysis of pharmacological effect of HN derivatives on AI) model mice. We found that the JAK2/STAT3 signaling axis mediates the anti-AD effect of HN/HNR. We also identified an 4 kDa HN-like molecule in testes and colons which can be transcriptionally regulated by lutenizing hormone (LH) or human chorionic gonadotropin (hCG). Moreover we found that intranasally administered Colivlein (CLN), the most potent HN derivative, completely suppressed memory impairment in a most common AD model termed Tg2576 (an APPswe transgenic mouse). In addition, we generated a novel AD model by crossing Tg2576 with HNR knockout mice and found that the mice developed memory impairment earlier than authentic Tg2576, supporting our hypothesis that HN/HNR function may play an important role in the pathogenesis of AD. This study provides a novel insight into therapy for AD.
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[Journal Article] Nasal Colivelin Treatment Ameliorates Memory Impairment Related to Alzheimer's Disease2008
Author(s)
Yamada, M, Chiba, T, Sasabe, J, Terashita, K, Aiso, S, Matsuoka, M
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Journal Title
Neuropsychopharmacology (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Anti-Apoptotic Action of Wnt5a in Dermal Fibroblasts Is Mediated by the PKA Signaling Pathway2008
Author(s)
Torii, K, Nishizawa, K, Kawasaki, A, Yamashita, Y, et. al., Matsuoka, M
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Journal Title
Cell Signal 20
Pages: 1256-1266
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Wnt5a promotes adhesion of human dermal fibroblasts by triggering a phosphatidylinositol-3 kinase/Akt signal2007
Author(s)
Kawasaki, A, Torii, K, Yamashita, Y, Nishizawa, K, Kanekura, K, et. al., Matsuoka, M
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Journal Title
Cell Signal 19
Pages: 2498-2506
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Antidepressant-like effect of Cordyceps sinensis in the mouse tail suspension test2007
Author(s)
Nishizawa, K, Torii, K, Kawasaki, A, Katada, M, Ito, M, Terashita, K, et. al., Matsuoka, M
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Journal Title
Biol Pharm Bull 30
Pages: 1758-1762
Description
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[Presentation] The JAK2/STAT3 signaling axis mediates therapeutic effect of Colivelin on memory impairment related to Alzheimer's disease2008
Author(s)
Yamada, M, Chiba, T, Sasabe, J, Terashita, K, Matsuoka, M, Aiso, S
Organizer
The 81th Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Yokohama
Year and Date
2008-03-17
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The JAK2/STAT3 signaling axis regulates memory in Alzheimer's disease2007
Author(s)
Chiba, T, Yamada, M, Sasabe, J, Terashita, K, Aiso, S, Matsuoka, M
Organizer
Society for Neuroscience 37th Annual Meeting 2007
Place of Presentation
San Diego
Year and Date
2007-11-06
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Nasal Colivelin treatment for Alzheimer's disease-related memory impairment2007
Author(s)
Yamada, M, Chiba, T, Sasabe, J, Terashita, K, Aiso, S, Matsuoka, M
Organizer
Society for Neuroscience 37th Annual Meeting 2007
Place of Presentation
San Diego
Year and Date
2007-11-03
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Development of a femtomolar-acting Humanin derivative named Colivelin By attaching ADNF to its N terminus : characterization of Colivelin-Mediated neuroprotection against Alzheimer's disease-relevant insults in vitro and in vivo2007
Author(s)
Yamada, M, Chiba, T, Sato, M, Sasabe, J, Terashita, K, Also, S, Nishimoto, I, Matsuoka, M
Organizer
The 16th The Japanese Youg Researcher's Society of Neurobehavioral Pharmacology
Place of Presentation
Nagoya
Year and Date
2007-03-13
Description
「研究成果報告書概要(欧文)」より
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