Effects of Synthetic Ligands on Heterodimer Pairs Regarding Full-Length Human PPARα, RXRα and LXRα
Steven Berberich (Committee Member), Weiwen Long (Committee Member), Lawrence Prochaska (Committee Member), Dean Rider, Jr. (Advisor)
Master of Science (MS)
Nuclear receptor study is critically relevant in therapeutic medicine since the intricate details of disease states pertaining to atherosclerosis and diabetes are poorly understood. Three nuclear receptors of interest regulate target genes pertaining to cholesterol and fatty acid regulation, linking these receptors to therapeutic medicine. The first is the peroxisome proliferator-activated receptor alpha (PPARa), which resides in liver and muscle, coordinating lipoprotein and fatty acid homeostasis . Cholesterol homeostasis is dictated by the liver X receptor alpha (LXRa), targeting genes pertaining to the kidney, intestine, liver and adipose tissues . A common partner receptor to PPARa and LXRa is known as the retinoid X receptor alpha (RXRa) . Although each receptor appears unique in function, the cause and effects of disease states are poorly understood due to the promiscuous nature of these receptor proteins. These particular receptors can form permissive heterodimers where metabolic effects can be manipulated by ligands . Accordingly, clinical care becomes increasingly complex as synthetic ligands made to target one receptor could have additional repercussions. With respect to therapeutic medicine, ligand binding may not be exclusive. Therefore, it becomes necessary to study synthetic ligands with each receptor, individually and in heterodimeric form, to further understand the complex regulation and clinical implications of synthetic ligands on disease states such as atherosclerosis and diabetes.
Department or Program
Department of Biochemistry and Molecular Biology
Year Degree Awarded
Copyright 2016, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.