Abstract |
We studied the blood-brain barrier (BBB) permeability and intracellular localization of a fluorescein isothiocyanate ( FITC)-labeled dieckol (1) 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.
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Authors | Jong Hwan Kwak, Zhigang Yang, Byungkwon Yoon, Yanxia He, Soojin Uhm, Hyeon-Cheol Shin, Bong Ho Lee, Yung Choon Yoo, Kyung Bok Lee, Seung-Yun Han, Jong Seung Kim |
Journal | Biomaterials
(Biomaterials)
Vol. 61
Pg. 52-60
(Aug 2015)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 25996411
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Benzofurans
- Fluorescent Dyes
- Reactive Oxygen Species
- dieckol
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Topics |
- Animals
- Benzofurans
(administration & dosage, pharmacokinetics)
- Blood-Brain Barrier
- Capillary Permeability
(drug effects, physiology)
- Cell Line
- Endoplasmic Reticulum
(drug effects, metabolism)
- Fluorescent Dyes
(chemistry)
- Humans
- Male
- Neurons
(drug effects, metabolism)
- Oxidative Stress
(drug effects, physiology)
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
(metabolism)
- Signal Transduction
(drug effects, physiology)
- Staining and Labeling
(methods)
- Subcellular Fractions
(drug effects, metabolism)
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