Development of amyloid beta C-terminal motifs conjugated with phenolic antioxidant
Project/Area Number |
26460153
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Drug development chemistry
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Research Institution | Showa University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
OHNO Akiko 国立医薬品食品衛生研究所, 安全性予測評価部, 主任研究官 (70356236)
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Project Period (FY) |
2014-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | アルツハイマー病治療薬 / アミロイドβ / 抗酸化物質 / トロロックス / カフェ酸 / アルツハイマー病 / ビタミンE / ペプチドモチーフ / 凝集阻害 / 神経細胞毒性抑制作用 / アミロイド |
Outline of Final Research Achievements |
The aggregation pathway of β-amyloid (Aβ) is a key target to prevent the onset of Alzheimer’s diseases (AD). The aggregation of the 42-mer peptides (Aβ42) induces the oxidative stress which is related to neurotoxicity. We synthesized Aβ42 C-terminal motifs (Aβn-42) conjugated to the antioxidant trolox (Tx) or caffeic acid (Ca). These compounds showed anti-aggregation activities toward Aβ42. The most potent inhibitory activity was found in Tx-Aβ36-42 and CA-Aβ38-42. Protective effects against Aβ42 induced neurotoxicity was also shown by TxAβ36-42 and CaAβ38-42. These compounds demonstrated potent antioxidative activities toward Aβ42-induced intracellular ROS generation. Finally, conjugating C-terminal motif to Trolox and caffeic acid is proved to be crucial for the protective effects on Aβ-induced neurotoxicity. TxAβ36-42 and CaAβ38-42 may be a starting point for the future development of drugs that prevent neurotoxicity and deposition of Aβ in the brain of AD.
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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Design, synthesis, and evaluation of Trolox-conjugated amyloid-beta C-terminal peptides for therapeutic intervention in an in vitro model of Alzheimer's disease2016
Author(s)
Takuya Arai, Akiko Ohno, Kazunori Mori, Taeko Kakizawa, Hiroshi Kuwata, Toshihiko Ozawa, Motoko Shibanuma, Shuntaro Hara, Seiichi Ishida, Masaaki Kurihara, Naoki Miyata, Hidehiko Nakagawa, Kiyoshi Fukuhara
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Journal Title
Bioorg. Med. Chem.
Volume: 24
Issue: 18
Pages: 4138-4143
DOI
Related Report
Peer Reviewed
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[Journal Article] Inhibition of amyloid fibril formation and cytotoxicity by caffeic acid-conjugated amyloid-beta C-terminal peptides2016
Author(s)
Takuya Arai, Akiko Ohno, Kazunori Mori, Hiroshi Kuwata, Mirei Mizuno, Kohei Imai, Shuntaro Hara, Motoko Shibanuma, Masaaki Kurihara, Naoki Miyata, Hidehiko Nakagawa, Kiyoshi Fukuhara
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 26
Issue: 22
Pages: 5468-5471
DOI
Related Report
Peer Reviewed
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[Journal Article] A double bond-conjugated dimethylnitrobenzene-type photolabile nitric oxide donor with improved two-photon cross section2015
Author(s)
1.N. Ieda, K. Hishikawa, K. Eto, K. Kitamura, M. Kawaguchi, T. Suzuki, K. Fukuhara, N. Miyata, T. Furuta, J. Nabekura, H. Nakagawa
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Journal Title
Bioorg. Med. Chem. Lett.
Volume: 25
Issue: 16
Pages: 3172-3175
DOI
Related Report
Peer Reviewed / Open Access
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