Orally Administered Benzofuran Derivative Disaggregated Aβ Plaques and Oligomers in the Brain of 5XFAD Alzheimer Transgenic Mouse

Da Won Kim, Gi Hun Bae, Hye Yun Kim, Hanna Jeon, Kyeonghwan Kim, Jisu Shin, Sunhee Lee, Seungpyo Hong, Ikyon Kim, Young Soo Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Amyloid-β (Aβ) aggregated forms are highly associated with the onset of Alzheimer's disease (AD). Aβ abnormally accumulates in the brain and induces neuronal damages and symptoms of AD such as cognitive impairment and memory loss. Since an antibody drug, aducanumab, reduces Aβ aggregates and delays clinical decline, clearance of accumulated Aβ in the brain is accounted as a therapeutic approach to treat AD. In this study, we synthesized 17 benzofuran derivatives that may disaggregate Aβ oligomers and plaques into inert monomers. By a series of Aβ aggregation inhibition and aggregates' disaggregation assays utilizing thioflavin T assays and gel electrophoresis, YB-9, 2-((5-methoxy-3-(4-methoxyphenyl)benzofuran-6-yl)oxy)acetic acid, was selected as the final Aβ-disaggregator candidate. When it was orally administered to the 8-month-old male transgenic mouse model with five familial AD mutations (5XFAD) via drinking water daily for two months, Aβ oligomers and plaques in hippocampus were reduced. Consequently, decreased astrogliosis and rescued synaptic dysfunction were observed in the hippocampus of YB-9-treated 5XFAD mice compared with the untreated transgenic control group.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalACS Chemical Neuroscience
Volume12
Issue number1
DOIs
Publication statusPublished - 2021 Jan 6

Bibliographical note

Funding Information:
This work was supported by Korea Health Industry Development Institute (KHIDI, HI18C0836), National Research Foundation of Korea (NRF-2018R1A6A1A03023718, NRF-2018R1D1A1B07048857, NRF-2018M3C7A1021858, and NRF-2020R1A2C2005961), and POSCO TJ Foundation (POSCO Science Fellowship).

Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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