Document Detail


Xanthene food dye, as a modulator of Alzheimer's disease amyloid-beta peptide aggregation and the associated impaired neuronal cell function.
MedLine Citation:
PMID:  21998691     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia. AD is a degenerative brain disorder that causes problems with memory, thinking and behavior. It has been suggested that aggregation of amyloid-beta peptide (Aβ) is closely linked to the development of AD pathology. In the search for safe, effective modulators, we evaluated the modulating capabilities of erythrosine B (ER), a Food and Drug Administration (FDA)-approved red food dye, on Aβ aggregation and Aβ-associated impaired neuronal cell function.
METHODOLOGY/PRINCIPAL FINDINGS: In order to evaluate the modulating ability of ER on Aβ aggregation, we employed transmission electron microscopy (TEM), thioflavin T (ThT) fluorescence assay, and immunoassays using Aβ-specific antibodies. TEM images and ThT fluorescence of Aβ samples indicate that protofibrils are predominantly generated and persist for at least 3 days. The average length of the ER-induced protofibrils is inversely proportional to the concentration of ER above the stoichiometric concentration of Aβ monomers. Immunoassay results using Aβ-specific antibodies suggest that ER binds to the N-terminus of Aβ and inhibits amyloid fibril formation. In order to evaluate Aβ-associated toxicity we determined the reducing activity of SH-SY5Y neuroblastoma cells treated with Aβ aggregates formed in the absence or in the presence of ER. As the concentration of ER increased above the stoichiometric concentration of Aβ, cellular reducing activity increased and Aβ-associated reducing activity loss was negligible at 500 µM ER.
CONCLUSIONS/SIGNIFICANCE: Our findings show that ER is a novel modulator of Aβ aggregation and reduces Aβ-associated impaired cell function. Our findings also suggest that xanthene dye can be a new type of small molecule modulator of Aβ aggregation. With demonstrated safety profiles and blood-brain permeability, ER represents a particularly attractive aggregation modulator for amyloidogenic proteins associated with neurodegenerative diseases.
Authors:
H Edward Wong; Inchan Kwon
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-10-05
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-10-14     Completed Date:  2012-02-13     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e25752     Citation Subset:  IM    
Affiliation:
Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / metabolism*
Amyloid beta-Peptides / chemistry*,  toxicity*
Cell Line, Tumor
Dose-Response Relationship, Drug
Erythrosine / pharmacology*
Food Coloring Agents / pharmacology*
Humans
Neurons / drug effects*,  metabolism,  pathology
Oxidation-Reduction / drug effects
Peptide Fragments / chemistry*,  toxicity*
Protein Multimerization / drug effects*
Protein Structure, Secondary
alpha-Synuclein / chemistry
Grant Support
ID/Acronym/Agency:
R21 NS069946/NS/NINDS NIH HHS; R21NS069946/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Food Coloring Agents; 0/Peptide Fragments; 0/alpha-Synuclein; 0/amyloid beta-protein (1-40); 16423-68-0/Erythrosine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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