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Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model

Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-β (Aβ) peptides in the brain. Accumulated Aβ in soluble oligomer and insoluble plaque forms are considered to be a pathological culprit and biomarker of the disorder. Here, we...

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Autores principales: Kim, DaWon, Lee, Jeong Hwa, Kim, Hye Yun, Shin, Jisu, Kim, Kyeonghwan, Lee, Sejin, Park, Jinwoo, Kim, JinIkyon, Kim, YoungSoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757811/
https://www.ncbi.nlm.nih.gov/pubmed/33362250
http://dx.doi.org/10.1371/journal.pone.0243041
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author Kim, DaWon
Lee, Jeong Hwa
Kim, Hye Yun
Shin, Jisu
Kim, Kyeonghwan
Lee, Sejin
Park, Jinwoo
Kim, JinIkyon
Kim, YoungSoo
author_facet Kim, DaWon
Lee, Jeong Hwa
Kim, Hye Yun
Shin, Jisu
Kim, Kyeonghwan
Lee, Sejin
Park, Jinwoo
Kim, JinIkyon
Kim, YoungSoo
author_sort Kim, DaWon
collection PubMed
description Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-β (Aβ) peptides in the brain. Accumulated Aβ in soluble oligomer and insoluble plaque forms are considered to be a pathological culprit and biomarker of the disorder. Here, we report a fluorescent universal Aβ-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Aβ monomers, dimers, and plaques. We synthesized a library of 26 fluorescence chemicals with the indolizine core and screen them through a series of in vitro tests utilizing Aβ as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Aβ plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Aβ oligomers within brain lysates of the mouse model under a fluorescence plate reader. Among oligomers aggregated from monomers and synthetic dimers from chemically conjugated monomers, YI-13 preferred the dimeric Aβ.
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spelling pubmed-77578112021-01-06 Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model Kim, DaWon Lee, Jeong Hwa Kim, Hye Yun Shin, Jisu Kim, Kyeonghwan Lee, Sejin Park, Jinwoo Kim, JinIkyon Kim, YoungSoo PLoS One Research Article Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-β (Aβ) peptides in the brain. Accumulated Aβ in soluble oligomer and insoluble plaque forms are considered to be a pathological culprit and biomarker of the disorder. Here, we report a fluorescent universal Aβ-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Aβ monomers, dimers, and plaques. We synthesized a library of 26 fluorescence chemicals with the indolizine core and screen them through a series of in vitro tests utilizing Aβ as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Aβ plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Aβ oligomers within brain lysates of the mouse model under a fluorescence plate reader. Among oligomers aggregated from monomers and synthetic dimers from chemically conjugated monomers, YI-13 preferred the dimeric Aβ. Public Library of Science 2020-12-23 /pmc/articles/PMC7757811/ /pubmed/33362250 http://dx.doi.org/10.1371/journal.pone.0243041 Text en © 2020 Kim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kim, DaWon
Lee, Jeong Hwa
Kim, Hye Yun
Shin, Jisu
Kim, Kyeonghwan
Lee, Sejin
Park, Jinwoo
Kim, JinIkyon
Kim, YoungSoo
Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
title Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
title_full Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
title_fullStr Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
title_full_unstemmed Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
title_short Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
title_sort fluorescent indolizine derivative yi-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5xfad alzheimer transgenic mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757811/
https://www.ncbi.nlm.nih.gov/pubmed/33362250
http://dx.doi.org/10.1371/journal.pone.0243041
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