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ACS Chemical Neuroscience

ACS Chemical Neuroscience

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Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains

Published:24 April 2019 DOI: 10.1021/acschemneuro.9b00093 PMID: 31016960
Naewoo Neo Shin, Hanna Jeon, Youngeun Jung, Seungyeop Baek, Sejin Lee, Hee Chan Yoo, Gi Hun Bae, Keunwan Park, Seung-Hoon Yang, Jung Min Han, Ikyon Kim*, YoungSoo Kim*

Abstract

Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer’s disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer’s patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-β aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-β aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-β plaques in brain sections of APP/PS1 double transgenic Alzheimer’s mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-β imaging agents for early stage Alzheimer’s.

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Procduct Name CAS Molecular Formula Supplier Price
1,4-Naphthoquinone 130-15-4 C10H6O2 512 suppliers $16.00-$6417.99
Amyloid β-Protein (2-42) 1678416-22-2 15 suppliers Inquiry

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