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

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.
AuthorsJong 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
JournalBiomaterials (Biomaterials) Vol. 61 Pg. 52-60 (Aug 2015) ISSN: 1878-5905 [Electronic] Netherlands
PMID25996411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Benzofurans
  • Fluorescent Dyes
  • Reactive Oxygen Species
  • dieckol
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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