Development of Alzheimer's disease drug candidates promoting Aβ clearance activity of type 2 microglia
| Project/Area Number |
21790114
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Drug development chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
KAWAHARA Kohichi Kumamoto University, 大学院・生命科学研究部, 助教 (10347015)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | アルツハイマー病 / ミクログリア / CD36 / レチノイド / インターロイキン-4 / 2型ミクログリア / インターロイキン4 / レチノイン酸受容体 / レチノイドX受容体 / モルヒネアナローグ / アミロイドβ |
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| Research Abstract |
As a new strategy for treatment of Alzheimer's disease (AD), we aimed to induce the antiinflammatory activity we have in a living body. In particular, we tried to develop the strategy for which the neuroprotective anti-inflammatory type of microglia (type 2 MG) is utilized aggressively and searched the new medicine seeds which achieves this. When we administered an intracerebral microinjection of a mixture of IL-4 and IL-13 into one hemisphere of 4.5 mo old APP23 mice, CD36-positive MG was induced at 2 day, and A β accumulation was reduced at 7 day post injection. The cytokine-induced CD36 expression was observed in arginase I-positive and Ym1-positive cells, which indicates that CD36-positive MG are M2-like cells (Kawahara et al., submitted). We found that oral administration of retinoic acid receptor agonist Am80, which increased IL-4 production in T-cell system, decreased brain Aβ42 peptide in APP23 mice (Kawahara et al., Biol. Pharm. Bull., 2009). This study may encourage development of new anti-inflammatory strategies for treatment of AD.
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] Oxidized LDL and lysophosphatidylcholine stimulate plasminogen activator inhibitor-1 expression through reactive oxygen species generation and ERK1/2 activation in 3T3-L1 adipocytes,2011
Author(s)
Kuniyasu, A., Tokunaga, M., Yamamoto, T., Inoue, S., Obama, K., Kawahara, K., Nakayama, H.
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Journal Title
Biochim Biophys Acta. 1811
Pages: 153-162
Related Report
Peer Reviewed
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[Journal Article] Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain β-amyloid peptides in APP23 mice2009
Author(s)
Kawahara, K., Nishi, K., Suenobu, M., Ohtsuka, H., Maeda, A., Nagatomo, K., Kuniyasu, A., Staufenbiel, M., Nakagomi, M., Shudo, K., Nakayama, H.
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Journal Title
Biol.Pharm.Bull. 32
Pages: 1307-1309
Related Report
Peer Reviewed
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[Journal Article] Marked induction of inducible nitric oxide synthase and tumor necrosis factor-a in rat CD40+ microglia by comparison to CD40- microglia.2009
Author(s)
Kawahara, K., Yoshida, A., Koga, K., Yokoo, S., Kuniyasu, A., Gotoh, T., Sawada, M., Nakayama, H.
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Journal Title
J.Neuroimmunol. 208
Pages: 70-79
Related Report
Peer Reviewed
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[Journal Article] A synthetic approach to develop peptide inhibitors delective for brain-type sodium channels on the basis of pompilidotoxin structure.2009
Author(s)
Yokote, S., Setoguchi, R., Shimizu, E., Kawahara, K., Kuniyasu, A., Shirasaki, T., Takahama, K., Konno, K., Kawai, N., Yamaoka, K., Kinoshita, E., Nakayama H.
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Journal Title
Heterocycles 79
Pages: 925-933
Related Report
Peer Reviewed
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