2008 Fiscal Year Final Research Report
Development of a novel Alzheimer's disease drug utilizing neuroprotective action of activated microglia
| Project/Area Number |
19390031
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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 |
Drug development chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
KAWAHARA Kohichi Kumamoto University, 大学院・医学薬学研究部, 助教 (10347015)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Makoto 熊本大学, 医学薬学研究部, 教授 (50207792)
KUNIYASU Akihiko 熊本大学, 医学薬学研究部, 准教授 (90241348)
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| Project Period (FY) |
2007 – 2008
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| Keywords | アルツハイマー病 / ミクログリア / インターロイキン-4 / レチノイド |
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| Research Abstract |
我々は、アルツハイマー病(AD)の新しい治療方策として生体に備わった抗炎症能力を誘導・賦活化すること、特に抗炎症性の神経保護型ミクログリア(2型MG)を積極的に活用する戦略と、これを実現する薬物シーズの開発を行った。(1) in vitroにおける2型MGによる・アミロイド(A・)クリアランスの分子機構を解明した(J. Immunol., 2008)。(2) (1)のA・クリアランス能がin vivoでも作動するかを、本病態モデルの一つAPP23マウスを用い、脳内にサイトカインを微量注入して調べた結果、A・蓄積が有意に認められる4.5月齢では、蓄積A・の減少とこれに伴う記憶学習能の有意な改善を認めることができた。(3) IL-4分泌促進能をもつある種の薬物候補化合物(経口投与)を用いても、APP23における脳内Aβ_42量が減少するとの予備知見も得た。
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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- microglia2009
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
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 structure2009
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
Peer Reviewed
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[Journal Article] Linkage between Phosphorylation of the Origin Recognition Complex and Its ATP Binding Activity in Saccharomyces cerevisiae2009
Author(s)
Makise, M., Takehara, M., Kuniyasu, A., Matsui, N., Nakayama, H., Mizushima, T.
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Journal Title
J. Biol. Chem 284
Pages: 3396-3407
Peer Reviewed
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[Journal Article] Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides, in mammalian cells2008
Author(s)
Kaneko, K., Akuta, T., Sawa, T., Kim, H. W., Fujii, S., Okamoto, T., Nakayama, H., Ohigashi, H., Murakami, A., Akaike, T.
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Journal Title
Cancer Lett 262
Pages: 239-247
Peer Reviewed
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[Journal Article] Subdomain IIIA of dog albumin contains a binding site similar to site II of human albumin2008
Author(s)
Kaneko, K., Fukuda, H., Chuang, V. T., Yamasaki, K., Kawahara, K., Nakayama, H., Suenaga, A., Maruyama, T., Otagiri, M.
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Journal Title
Drug Metab. Dispos 36
Pages: 81-86
Peer Reviewed
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[Journal Article] Combinatorial targeting of the macropinocytotic pathway in Leukemia and lymphoma cells2008
Author(s)
Nishimura, S., Takahashi, S., Kamikatahira, H., Kuroki, Y., Jaalouk, D. E., O'Brien, S., Koivunen, E., Arap, W., Pasqualini, R., Nakayama, H., Kuniyasu, A.
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Journal Title
J. Biol. Chem 283
Pages: 11752-11762
Peer Reviewed
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[Journal Article] Constitutive overexpression of P-glycoprotein, rather than breast cancer resistance protein or organic cation transporter 1, contributes to acquisition of imatinib-resistance in K562 cells2008
Author(s)
Hirayama, C., Watanabe, H., Nakashima, R., Nanbu, T., Hamada, A., Kuniyasu, A., Nakayama, H., Kawaguchi, T., Saito, H.
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Journal Title
Pharm. Res 25
Pages: 827-835
Peer Reviewed
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