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 language | English |
|---|---|
| Pages (from-to) | 3031-3044 |
| Number of pages | 14 |
| Journal | ACS Chemical Neuroscience |
| Volume | 10 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2019 Jun 19 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Physiology
- Cognitive Neuroscience
- Cell Biology
Cite this
}
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, Vol. 10, No. 6, 19.06.2019, p. 3031-3044.Research output: Contribution to journal › Article
TY - JOUR
T1 - Fluorescent 1,4-Naphthoquinones to Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains
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
PY - 2019/6/19
Y1 - 2019/6/19
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85065497388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065497388&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.9b00093
DO - 10.1021/acschemneuro.9b00093
M3 - Article
C2 - 31016960
AN - SCOPUS:85065497388
VL - 10
SP - 3031
EP - 3044
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
SN - 1948-7193
IS - 6
ER -