Fluorescent indolizine derivative YI-13 detects amyloid-ß monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model.
PLoS One
; 15(12): e0243041, 2020.
Article
en En
| MEDLINE
| ID: mdl-33362250
ABSTRACT
Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-ß (Aß) peptides in the brain. Accumulated Aß 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 Aß-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Aß 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 Aß as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Aß plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Aß 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 Aß.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Péptidos beta-Amiloides
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Enfermedad de Alzheimer
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Indolizinas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
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MEDICINA
Año:
2020
Tipo del documento:
Article