2007 Fiscal Year Final Research Report Summary
Investigation on TGFbeta2 involvement in Alzheimer's disease's related neuronal death and Humanin signal transduction as an endogenous anti-Alzheimer's disease's defense factor
| Project/Area Number |
18390077
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
MATSUOKA Masaaki Keio University, School of Medicine, Associate Professor (70222297)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Tomohiro KEIO University, School of Medicine, Assistant Professor (60398617)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Alzheimer's disease / TGFbeta2 / Neuronal cell death / Colivelin / Defense factor / Humanin |
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| Research Abstract |
In our earlier studies, we demonstrated that TGFbeta2 is a putative natural ligand of APP inducing Alzheimer's disease's related neuronal death (TGFbeta2 theory) and Humanin may be a specific endogenous neuroprotective polypeptide inhibiting Alzheimer's disease's relevant neuronal death (defense theory). The first purposes of this project have been to obtain evidence supporting the TGFbeta2 theory of Alzheimer's disease's related neuronal cell death and the defense theory of Alzheimer's disease. The second purpose has been to conduct preclinical research to develop Humanin or a Humanin's derivative Colivelin as neuroprotective drugs to Alzheimer's disease. Using immunohistochemistry and molecular biological techniques, we have first shown that TGFbeta2 expression levels were upregulated in brains of autopsied Alzheimer's disease cases. In addition, we have identified MOCA and POSH as a putative mediators linking PS1 and the TGFbeta2-triggered death signal pathway. These results strongly support our TGFbeta2 theory. Second, we identified a Humanin receptor on the cell membrane and elucidated that in addition to the JAK2/STAT3 pathway, a PI3 kinase pathway was activated by Humanin. Identifing 4k1) and 10kD endogenous Humanin-like peptides, we are also now trying to identify the primary structure of endogenous Humanin-like peptides. Finally, we have succeeded in showing that Colivelin inhibits memory impairment in Alzheimer's disease transgenic mouse models Tg2576 mice aged 15 months. All these results indicated that Humanin or Humanin-like peptides exist as an endogenous defense factor and that neuroprotective therapy with Humanin may be effective against Alzheimer's disease.
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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] Nasal ColivelinTreatment Ameliorates Memory Impairment Related to Alzheimer'sDisease.2008
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] Aiso S. D-Serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis2007
Author(s)
Sasabe, J, Chiba, T, Yamada, M, Okamoto, K, Nishimoto, I, Matsuoka, M
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Journal Title
EMBO J 26
Pages: 4149-4159
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
「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] S-nitrosothiol depletion in amyotrophic lateral sclerosis2006
Author(s)
Schonhoff, CM, Matsuoka, M, et. al., Gaston, B, Macdonald, T, Xu, Z, Mannick, J
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Journal Title
Proc. Natl Acad Sci USA
Pages: 103-7 : 2404-2409
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Transforming growth factor beta2 autocrinally mediates neuronal cell death induced by amyloid-b2006
Author(s)
Hashimoto, Y, Nawa, M, Chiba, T, Aiso, S, Nishimoto, I, Matsuoka, M
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Journal Title
J Neurosci Res 83-6
Pages: 1039-1047
Description
「研究成果報告書概要(欧文)」より
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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 81 th 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] Amyotrophic lateral sclerosis-linked pro56ser vesicle-associated membrane protein-associated protein impairs unfolded protein response.2007
Author(s)
Kanekura, K, Suzuki, H, Nishimoto, I, Levine, T, Kohno, K, Suzuki, N, Aiso, S, Matsuoka, M
Organizer
18th International Symposia on ALS/MND (motor neuron disease)
Place of Presentation
Toronto, Canada
Year and Date
2007-12-01
Description
「研究成果報告書概要(欧文)」より
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[Presentation] D-serine exacerbates glutamate excitotoxicity in ALS2007
Author(s)
Sasabe, J, Chiba, T, Yamada, M, Okamoto, K, Nishimoto, I, Aiso, S, Matsuoka, M
Organizer
18th International Symposia on ALS/MND (motor neuron disease)
Place of Presentation
Toronto, Canada
Year and Date
2007-12-01
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 ameliorates Alzheimer's cognitive deficits via the JAK2/STAT3 axis2007
Author(s)
Yamada, M, Chiba, T, Sasabe J, Sato, M, Nishimoto, IAiso, S, Matsuoka, M
Organizer
The 80th Annual Meeting of the Japanese Pharmacological Society
Place of Presentation
Nagoya
Year and Date
2007-03-16
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 Colive attaching ADNF to its N terminus : characterization of Colivelin-mediate neuroprotection against Alzheimer's disease-relevant insults in vitro ar vivo2007
Author(s)
Yamada, M, Chiba, T, Sato, M, Sasabe, J, Terashita, K, Aiso, 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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[Presentation] Nasal Colivelin treatment ameliorates Alzheimer's cognitive deficits via the JAK2/STAT3 axis2007
Author(s)
Matsuoka, M, Yamada, M, Chiba, T, Sasabe, J, Sato, M, Nishimoto, I, Aiso, S
Organizer
Keystone symposia : Molecular mechanisms of neurodegeneration
Place of Presentation
Taos, New Mexico
Year and Date
2007-01-19
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Characterization of Colivelin-mediated neuroprotection against ALS -relevant insults2006
Author(s)
Chiba, T, Yamada, M, Sasabe, J, Nishimoto, I, Aiso, S, Matsuoka, M
Organizer
International Symposia on ALS/MND (motor neuron disease)
Place of Presentation
Yokohama
Year and Date
2006-12-01
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Elimination of apoptosis signal-regulating kinase 1 gene from ALS model mice attenuates disease progression2006
Author(s)
Sasabe, J, Chiba, T, Yamada, M, Nishimoto, I, Aiso, S, Matsuoka, M
Organizer
International Symposia on ALS/MND (motor neuron disease)
Place of Presentation
Yokohama
Year and Date
2006-12-01
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Intranasally administered Colivelin exhibits neuroprotective effect on cholinergic neurons via the JAK/STAT axis2006
Author(s)
Chiba, T, Yamada, M, Sasabe, J, Sato, M, Nishimoto, I, Aiso, S, Matsuoka, M
Organizer
Society for Neuroscience 36th Annual Meeting 2006
Place of Presentation
Atlanta
Year and Date
2006-10-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Nasal Colivelin treatment ameliorates Alzheimer's congnitive deficits via the JAK/STAT axis2006
Author(s)
Yamada, M, Chiba, T, Sasabe, J, Sato, M, Nishimoto, I, Aiso S, Matsuoka, M
Organizer
Neuron and disease -The 4th Neuron Satellite Meeting 2006
Place of Presentation
Atlanta
Year and Date
2006-10-13
Description
「研究成果報告書概要(欧文)」より
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