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Neurodegenerative and Neuroprotective Cell Signaling Pathways

BethAnn McLaughlin
Department of Neurology and Pharmacology
8110A; MRB III
615-936-3847 (office)

My laboratory is interested in studying cell signaling pathways related to neurodegeneration and protection. We have two major research programs ongoing in the lab. The first is the study of how a short, sublethal ischemic event in the brain can lead to subsequent neuronal resistance to a severe stroke, a phenomenon commonly referred to as ischemic preconditioning. In order to investigate the cellular and molecular events that contribute to this process, we have developed several in vivo and in vitro systems in which cortical neuronal cells can be rendered less sensitive to excitotoxic cell death following a nontoxic exposure to mild chemical ischemia or hypoxia. We are using a variety of biochemical, molecular and proteomic approaches to both enhance our understanding of signaling pathways that we have already determined to be critical for the expression of preconditioning as well as to identify new protein targets which may contribute to this phenomenon. Our findings suggest that intervention against neurological events which result in subtoxic activation of traditional cell death pathways may actually increase vulnerability to subsequent stressors.

Other ongoing lab projects include understanding how classical biochemical changes in ion homeostasis (specifically zinc, calcium and potassium homeostasis) induce the molecular pathways associated with apoptotic cell death. In this work we established a novel link between ROS and zinc induced activation of MAPKs and opening of potassium channels that are associated with apoptotic cell death.

The goal of my research program is to understand the endogenous pathways associated with neurodegeneration and protection to develop novel therapeutics for stroke, cerebral palsy and other degenerative conditions. In addition, these studies investigate signaling pathways which provide protective mechanisms against other forms of cell death.

For more information, please visit the lab website.