University of Kentucky
101 Sanders-Brown Bldg.
800 S. Limestone Street
Lexington, KY 40536
Signal transduction, glia-neuron interactions, neuroinflammation, drug discovery for neurodegenerative disorders
Research in the Van Eldik lab aims to elucidate the mechanisms by which abnormal activation of glia in the brain, especially astrocytes and microglia, leads to damage of the neurons and progressive neurodegeneration in diseases like Alzheimer's disease (AD) and traumatic brain injury (TBI). The overall goal is to utilize knowledge of potentially "druggable" pathways to develop new therapeutics. The normal role of the glia is to cooperate with the neurons to keep the brain operating smoothly. When an injury or change in the brain occurs, the glial mount a beneficial inflammation response to fight off the insult and restore the brain to its proper functioning. While a controlled inflammatory response is an important element in protecting the brain, this beneficial process sometimes gets out of balance and the inflammation becomes too strong or does not shut off on schedule. In neurodegenerative diseases, the glia are over-activated, producing detrimental inflammatory molecules called proinflammatory cytokines that can contribute to nerve cell death and accelerate the progression of the disease. Although neuroinflammation appears to play a pivotal role in the development and progression of neurodegeneration, the molecular mechanisms underlying the process and approaches to downregulate the neuroinflammation have received little attention. This raises the logical question of whether drugs can be developed to selectively target cytokine up-regulation in glia,with the hope that such drugs would slow down or perhaps even prevent disease progression.
Projects in the Van Eldik lab are focused on identification of signal transduction pathways that mediate the neuroinflammatory responses of activated glia and exploration of how aberrant glial-neuronal interactions contribute to or influence neurodegenerative processes. In collaborative research with medicinal chemistry and integrative pharmacology colleagues, we have extended this knowledge of pathophysiology progression to drug discovery efforts that have yielded novel small molecules that are candidates for drug development as well as tools to explore the potential of improved neurologic outcomes by restoration of activated glia back towards homeostasis.