| dc.description.abstract | Alzheimer's Disease (AD) is a progressive neurodegenerative disease that is the most common form of dementia. It is expected that AD cases worldwide will exceed 100 million by 2050. There are two key pathologies to AD which are extracellular beta-amyloid (AB) plaques and intracellular hyperphosphorylated, neurofibrillary tau tangles. The main brain regions impacted by AD damage are the cerebral cortex and the hippocampus; areas that are in charge of learning and memory. The presence of the AB plaques can activate microglial cells in the brain. Microglial cells are macrophages in the central nervous system and are responsible for the innate immune response in the brain. Activation of these microglial cells can induce an inflammatory response and oxidative stress. Inflammation is a natural response to fighting off pathogens, however, chronic inflammation can be detrimental to tissues and this damage plays a pivotal role in neurodegeneration. Inflammation and oxidative stress are two hallmarks of AD pathogenesis and are connected. Dysfunction of the antioxidant system can cause accumulation of reactive oxygen species (ROS) which causes oxidative stress. The presence of ROS activates an inflammatory response leading to the production of proinflammatory mediators and cytokines. ROS and proinflammatory cytokines can lead to more AB plaques that cause more inflammation, thus, causing a self-perpetuating process. Previous research has shown that agents that lead to reduction in inflammation and oxidative stress are potential drug therapies for AD and other neurodegenerative disorders. This study was done in collaboration with Dr. Green's lab in the TCU Chemistry Department. Dr. Green has successfully created compounds, one being L4, that act as potent antioxidants. Prior studies have demonstrated that L4 has the capability to rescue BV2 microglial cells and increase cell survival during oxidative stress. This research aimed to examine the potential therapeutic properties of the antioxidant compound L4 against the inflammatory response in vitro, using BV2 microglial cells, following stimulation by lipopolysaccharide (LPS). LPS is a known element to induce inflammation in microglial cells. First, it was determined that LPS treatment can successfully induce the secretion of the proinflammatory cytokine TNF-alpha. This was done by treating cells with different concentrations of LPS for specific treatment periods. Next, the experiment was repeated, except cells were pretreated with the compound L4 for one hour before adding the LPS treatment. This was done to study the ability of L4 to block the proinflammatory cytokine production. The hypothesis was that L4 pretreatment would reduce proinflammatory cytokine production, however, the concentrations of L4 used in this study were likely not high enough to block the inflammatory response. Therefore, further research needs to be done to determine the appropriate concentration of the L4 that would be the most therapeutic against the inflammatory response. | |
