Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783626803869384704 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7757811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kimdawon fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT leejeonghwa fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT kimhyeyun fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT shinjisu fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT kimkyeonghwan fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT leesejin fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT parkjinwoo fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT kimjinikyon fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel AT kimyoungsoo fluorescentindolizinederivativeyi13detectsamyloidbmonomersdimersandplaquesinthebrainof5xfadalzheimertransgenicmousemodel |