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Transcript
Pharmacoproteomics: Visual Analytics of Protein Network Related to Acamprosate Efficacy
Kenneth Smith1, S. Burke1, U. Cvek1, M. Trutschl1, C. Germany2, Doo-Sup Choi3, Hyung W.
Nam2
1. LSU Shreveport, Department of Computer Science
2. LSU Health Shreveport, Department of Pharmacology, Toxicology and Neuroscience
3. Mayo Clinic College of Medicine, Department of Molecular Pharmacology and Psychiatry
Background and Objective
Acamprosate is an FDA-approved medication for the treatment of alcoholism that is only
effective in certain patients. Several clinical studies have identified glutamate and its receptormediated signaling pathways as regulating acamprosate efficacy in patients, but its
pharmacological action is not detailed yet.
Methods
Pharmacoproteomics followed by pharmacometabolomics is a potential method for determining
the molecular mechanism of acamprosate action according to the drug response. We
investigated the change in brain protein expression after acamprosate treatment using ethanol
preferring mice model.
Results
In this study, the label free proteomics was used to profile the protein in response to
acamprosate treatment during an ethanol self-administration period. Using statistical analysis,
we identified 1,040 proteins that significantly change in expression in the nucleus accumbens
among a total of 3,634 total proteins. We applied visual data analytics and pathway analysis to
identify RTN4, RHOA and NFkB signaling, which regulate immune function, and may play a role
in acamprosate effectiveness in mice.
Discussion and Conclusions
Our results provide a molecular basis for the effectiveness of acamprosate in the nucleus
accumbens, providing a better understanding of the pharmacological treatment of alcohol use
disorders in patients.
Grant Acknowledgment
Research reported in this abstract was partially supported by an Institutional Development
Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes
of Health under grant number P20GM103424 and COBRE award Number P30GM110703.