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Aryloxypropanolamine targets amyloid aggregates and reverses Alzheimer-like phenotypes in Alzheimer mouse models by Hee Yang Lee; Soljee Yoon; Jeong Hwa Lee; Keunwan Park; Youngeun Jung; Illhwan Cho; Donghee Lee; Jisu Shin; Kyeonghwan Kim; Sunmi Kim; Jimin Kim; Koeun Kim; Seung Hoon Han; Seong Muk Kim; Hye Ju Kim; Hye Yun Kim; Ikyon Kim; Young Soo Kim is a Medicine article available to read on EtoBox.
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## Abstract ## Background Aggregated amyloid-β (Aβ) is considered a pathogenic initiator of Alzheimer’s disease (AD), in strong association with tau hyperphosphorylation, neuroinflammation, synaptic dysfunction, and cognitive decline. As the removal of amyloid burden from AD patient brains by antibodies has shown therapeutic potential, the development of small molecule drugs inducing chemical dissociation and clearance of Aβ is compelling as a therapeutic strategy. In this study, we synthesized and screened aryloxypropanolamine derivatives and identified 1-(3-(2,4-di-tert-pentylphenoxy)-2-hydroxypropyl)pyrrolidin-1-ium chloride, YIAD002, as a strong dissociator of Aβ aggregates. ## Methods The dissociative activity of aryloxypropanolamine derivatives against Aβ aggregates were evaluated through in vitro assays. Immunohistochemical staining, immunoblot assays, and the Morris water maze were used to assess the anti-Alzheimer potential in YIAD002-treated 5XFAD and transgenic APP/PS1 mice. Target-ligand interaction mechanism was characterized via a combination of peptide mapping, fluorescence dissociation assays, and constrained docking simulations. ## Results Among 11 aryloxypropanola
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- Author
- Hee Yang Lee; Soljee Yoon; Jeong Hwa Lee; Keunwan Park; Youngeun Jung; Illhwan Cho; Donghee Lee; Jisu Shin; Kyeonghwan Kim; Sunmi Kim; Jimin Kim; Koeun Kim; Seung Hoon Han; Seong Muk Kim; Hye Ju Kim; Hye Yun Kim; Ikyon Kim; Young Soo Kim
- Publisher
- Springer Science and Business Media LLC
- Published
- 2022
- Language
- EN
- Field
- Medicine (Health Sciences)