| Budget Amount *help |
¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Outline of Final Research Achievements |
Aggregation of amyloid β42 (Aβ42) is one of the hallmarks of Alzheimer’s disease (AD). The mechanism of Aβ42 aggregation mainly consists of two phases, nucleation and elongation. Aβ42 oligomerization related to the elongation induces the neurotoxicity in AD pathogenesis. Herein we report that a preferable inhibition of toxic oligomer formation of Aβ42 by uncarinic acid C (UA-C), a triterpenoid from medicinal herbs, originates from a salt bridge of their carboxy groups with Aβ42-Lys16. We also proposed a method of classifying compounds into 9 groups based on their ability to modulate the nucleation and/or elongation phases. By screening natural product and shoyaku libraries or metabolomics, several compounds such as warfarin and quercetin 3-O-glucuronide that prevented Aβ42-induced neurotoxicity were identified. Moreover, we developed RNA aptamers with higher affinity toward Aβ42 oligomers, which strongly recognized brain oligomers.
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