2017 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Showa University |
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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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| 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 |
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| 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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| Free Research Field |
創薬化学
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