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

Authors
Shin, Naewoo NeoJeon, HannaJung, YoungeunBaek, SeungyeopLee, SejinYoo, Hee ChanBae, Gi HunPark, KeunwanYang, Seung-HoonHan, Jung MinKim, IkyonKim, YoungSoo
Issue Date
2019-06
Publisher
AMER CHEMICAL SOC
Citation
ACS CHEMICAL NEUROSCIENCE, v.10, no.6, pp.3031 - 3044
Abstract
Recent clinical approvals of brain imaging radiotracers targeting amyloid-beta 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-beta 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-beta aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-beta 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-beta imaging agents for early stage Alzheimer's.
Keywords
CYTOTOXIC ACTIVITIES; PROTEIN OLIGOMERS; CROSS-LINKING; BETA PLAQUES; DERIVATIVES; NAPHTHOQUINONES; ANTIBACTERIAL; INHIBITION; BINDING; MODEL; CYTOTOXIC ACTIVITIES; PROTEIN OLIGOMERS; CROSS-LINKING; BETA PLAQUES; DERIVATIVES; NAPHTHOQUINONES; ANTIBACTERIAL; INHIBITION; BINDING; MODEL; Alzheimer' s disease; amyloid; diffuse plaques; 1,4-naphthoquinone; imaging agent; A beta
ISSN
1948-7193
URI
https://pubs.kist.re.kr/handle/201004/119946
DOI
10.1021/acschemneuro.9b00093
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KIST Article > 2019
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