2012-2013 ARDRAF Project

Revealing the Effect of Food Dyes on Amyloid-Beta Structure-Cytotoxicity Relationships

VCoA

*The Virginia Center on Aging which administers the Alzheimer’s and Related Diseases Research Award Fund for the Commonwealth of Virginia, provides seed money to researchers in Virginia to stimulate innovative research into biomedical and psychosocial aspects of dementia, including cell biology, caregiving, and animal modeling.


 

Revealing the Effect of Food Dyes on Amyloid-Beta Structure-Cytotoxicity Relationships

Inchan Kwon, PhD and Erik Fernandez, PhD

University of Virginia  

REPORT:

Modulation of amyloid-beta (Aβ) peptide aggregation is considered a promising therapeutic strategy to cure Alzheimer’s disease (AD). Although several U.S. Food and Drug Administration (FDA)-approved drugs temporarily reduce symptoms, no treatment exists that slows or stops progression of AD. There is a need to discover more potent molecules and elucidate their relationship to AD pathology. In the search for safe, effective aggregation modulators, the investigators have examined FDA-approved food dyes and their close analogs. They previously reported that erythrosine B (ER) and brilliant blue G (BBG) reduce Aβ neurotoxicity by modulating Aβ aggregation. These exciting results duggest that ER and BBG could be promising lead compounds for AD therapy. For this project, the researchers explored the structural basis for ER and BBG (and their analogs) Aβ binding and the subsequent reduction of cytotoxicity. The preliminary results obtained indicate that a BBG analog, Brilliant Blue R, could be a promising candidate to proceed with in vivo testing in an animal model of AD. In addition, the immunoassays revealed the 10-16 amino acid sequence of the Aβ peptide as a potentially important binding region for aggregation modulators/inhibitors. This work could open the door for structure-based design of molecular or peptide inhibitors that specifically target the 10-16 amino acid sequence of Aβ. Lastly, the immunoassays described in this work provide an economical template for researchers to obtain residue level information without the need for nuclear magnetic resonance spectrometers or other costly apparatus.

 

(Dr. Kwon may be contacted at 434/243-1822, ik4t@virginia.edu; Dr. Fernandez may be contacted at 434/ 982-2658, ejf3c@virginia.edu)

 

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