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Blood-brain barrier-permeable fluorone-labeled dieckols acting as neuronal ER stress signaling inhibitors

Authors
Kwak, Jong HwanYang, ZhigangYoon, ByungkwonHe, YanxiaUhm, SoojinShin, Hyeon-CheolLee, Bong HoYoo, Yung ChoonLee, Kyung BokHan, Seung-YunKim, Jong Seung
Issue Date
8월-2015
Publisher
ELSEVIER SCI LTD
Keywords
Fluorone-labeled dieckols; Click reaction; Blood-brain barrier; Endoplasmic reticulum (ER) stress; ER localization
Citation
BIOMATERIALS, v.61, pp.52 - 60
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
61
Start Page
52
End Page
60
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/92933
DOI
10.1016/j.biomaterials.2015.04.045
ISSN
0142-9612
Abstract
We studied the blood-brain barrier (BBB) permeability and intracellular localization of a fluorescein isothiocyanate (FITC)-labeled dieckol (I) and a rhodamine B-labeled dieckol (7), for exploring the possible therapeutic application of fluorone-labeled dieckols in neurodegenerative diseases. Both compounds (1 & 7) were synthesized through a click reaction and were found to be localized in the endoplasmic reticulum (ER) of the two types of brain cell lines (SH-SY5Y and BV-2 cells) tested; they also reduced ER stress in the SH-SY5Y human neuroblastoma cells. In addition, 1 and 7 were shown to pass the BBB in rats upon intravenous administration. Altogether, our study demonstrates, for the first time, that targeted ER-stress reduction in brain cells can be achieved by introducing fluorone dieckol conjugates into systemic circulation. Therefore, 1 and 7 provide a novel and promising ER-targeting therapeutic strategy for neurodegenerative diseases. (C) 2015 Elsevier Ltd. All rights reserved.
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