(214c) Molecular Interaction of Erythrosine B and Its Variations With Amyloid ? Oligomer: Molecular Modeling Approach

Authors: 
Koo, D., Georgia Institute of Technology
Lee, J., Georgia Institute of Technology
Jang, S. S., Georgia Institute of Technology
Kwon, I., University of Virginia


Molecular Interaction of Erythrosine B and its variations with Amyloid β Oligomer: Molecular Modeling Approach

 

Doyeon Koo,* Juho Lee,* Euisun Pyo and Seung Soon Jang

Computational NanoBioTechnology (CNBT) Laboratory
School of Materials Science and Engineering, Georgia Institute of Technology

771 Ferst Drive, Atlanta, GA 30332-0245

Inchan Kwon

Department of Chemical Engineering, University of Virginia

102 Engineers’ Way, PO Box 400741
Charlottesville, VA 22904-4741

Alzheimer disease (AD) is the most common type of neurodegenerative disease which causes memory dysfunction, impaired judgment, and disorientation.[1] Although recent research has revealed a major pathological hallmark of AD, permanent treatment for AD is yet to be established for clinical use. Based on amyloid hypothesis, the AD treatment can be developed by investigating the formation of neuritic plaques composed of amyloid-β (Aβ) peptide fibrils from the cleavage of amyloid precursor protein (APP) by β- and γ-secretases[2]. Based on recent studies on AD, it has been discovered that small size of oligomer structure of Aβ42 peptide is known to be more toxic than fibril structure. Also, there is a difference in toxicity and aggregation between Aβ40 and Aβ42 peptides.[3]Therefore, the key point in finding an effective drug is the drug efficacy in dissociating the Aβ 42 peptides and preventing its aggregation.

In this molecular modeling study, Erythrosine B (ER), a Food and Drug Administration (FDA)-approved red food dye and its variations have been investigated to understand its mechanisms to hinder the aggregation of the Aβ peptides .[4]  The most favorite binding sites and the relative binding affinity were evaluated by Autodock  developed by the Scripps Institute, for monomeric strands and fiber units of Aβ40 and Aβ42, and subsequently the molecular dynamics simulations were performed to monitor the structural evolution of systems.

* They have equal contribution to this study.

References

[1]       Alzheimer’s Association. (2011) 2011 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia. 7(2): 21-23.

[2]       Masters, C.L. et al.(1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc.Natl. Acad. Sci. USA 82, 4245–4249

[3]       Ahmed, M. Davis, J. Aucoin, D. et all. (2010) Structural conversion of neurotoxic amyloid- β1-42 oligomers to fibrils. Nature structural & Molecular biology. 17. 561-567

[4]       Wong,H. Kwon, I. (2011) Xanthene Food Dye, as a Modulator of Alzheimer’s Disease Amyloid-beta Peptide Aggregation and the Associated Impaired Neuronal Cell Function. PLos One. 6(10).

[5]       Wong, H. Qi,W. Choi,H. Kwon, I. Fernandez, E.(2011) A Safe, Blood-Brain Barrier Permeable Triphenylmethane Dye Inhibits Amyloid-β Neurotoxicity by Generating Nontoxic Aggregates. ACS Chem. Neurosci. 2. 645–657

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