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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalACS Chemical Neuroscience
DOIs
Publication statusE-pub ahead of print - 2019 Apr 24

Fingerprint

Amyloid Plaques
Amyloid
Transgenic Mice
Brain
Imaging techniques
Blood-Brain Barrier
Neuroimaging
Biopsy
Pathology
Early Diagnosis
Autopsy
Alzheimer Disease
Scaffolds
Coloring Agents
Fluorescence
1,4-naphthoquinone
Assays
Agglomeration
Derivatives

Cite this

Neo Shin, Naewoo ; Jeon, Hanna ; Jung, Youngeun ; Baek, Seungyeop ; Lee, Sejin ; Yoo, Hee Chan ; Bae, Gi Hun ; Park, Keunwan ; Yang, Seung-Hoon ; Han, Jung Min ; Kim, Ikyon ; Kim, YoungSoo. / Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains. In: ACS Chemical Neuroscience. 2019.
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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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Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains. / Neo Shin, Naewoo; Jeon, Hanna; Jung, Youngeun; Baek, Seungyeop; Lee, Sejin; Yoo, Hee Chan; Bae, Gi Hun; Park, Keunwan; Yang, Seung-Hoon; Han, Jung Min; Kim, Ikyon; Kim, YoungSoo.

In: ACS Chemical Neuroscience, 24.04.2019.

Research output: Contribution to journalArticle

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AU - Neo Shin, Naewoo

AU - Jeon, Hanna

AU - Jung, Youngeun

AU - Baek, Seungyeop

AU - Lee, Sejin

AU - Yoo, Hee Chan

AU - Bae, Gi Hun

AU - Park, Keunwan

AU - Yang, Seung-Hoon

AU - Han, Jung Min

AU - Kim, Ikyon

AU - Kim, YoungSoo

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AB - 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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