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

First Author  Kim D Year  2020
Journal  PLoS One Volume  15
Issue  12 Pages  e0243041
PubMed ID  33362250 Mgi Jnum  J:300168
Mgi Id  MGI:6491349 Doi  10.1371/journal.pone.0243041
Citation  Kim D, et al. (2020) Fluorescent indolizine derivative YI-13 detects amyloid-beta monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model. PLoS One 15(12):e0243041
abstractText  Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-beta (Abeta) peptides in the brain. Accumulated Abeta 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 Abeta-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Abeta 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 Abeta as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Abeta plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Abeta 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 Abeta.
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