Center of Excellence for Research on CAM Antioxidant Therapies
Using cell culture studies and relevant animal models, this Center will determine the molecular and cellular mechanisms of action and in vivo safety and efficacy of selected antioxidant therapies in aging, amyotrophic lateral sclerosis (ALS, commonly known as Lou Gehrig's disease), and cardiovascular diseases (CVD). These goals will be accomplished through three highly interactive projects. Project 1 will investigate the hypothesis that metal chelators and dithiol compounds such as desferioxamine, EDTA, and lipoic acid, inhibit endothelial activation and, thus, atherosclerosis by preventing oxidative inactivation of redox-sensitive cellular signal transducers and subsequent induction of gene transcription by redox-sensitive transcription factors. Project 2 will determine the mechanisms of how lipoic acid improves transcriptional regulation of glutamylcysteine ligase gene expression and thus reverses the gene-related losses of cellular detoxication system. Project 3 will study the role of the antioxidant enzyme, superoxide dismutase, in the pathogenesis of ALS and how antioxidant therapies may modulate the progression of ALS through this enzyme.