| Abstract | Alzheimer's disease (AD) is ranked as the seventh leading cause of death in the US with over six million Americans currently diagnosed, and that number is projected to reach about 13 million by 2050. AD is currently believed to be caused by numerous factors ranging from genetics, lifestyle, and environmental conditions, but the exact pathogenesis of AD remains uncertain. What has been identified is the pathology associated with the disease includes the presence of amyloid beta (AB) plaques and neurofibrillary tangles composed of the protein tau in the brain. In cases of AD these proteins are misfolded and accumulate, causing disruptions in cell signaling and neuronal death, therefore worsening the disease. AB plaques also activate microglial cells, which produce cytokines and induce inflammation. Activation of an inflammasome protein, NLRP3, found in microglial cells, results in the production of the cytokine IL-1B which has been implicated in Alzheimer's due to its ability to induce and maintain this chronic cycle of inflammation, and possibly results in more amyloid-beta deposition. Studies have shown that the removal of NLRP3 results in decreased deposition of the proteins involved in AD. Our research examines novel anti-inflammatory drugs and their potential to reduce NLRP3-mediated inflammation-induced brain damage. We hypothesize that these drugs act to reduce inflammation by inhibiting a component of the NLRP3 inflammasome pathway. The levels of various proteins involved in the pathway were measured using Western Blot analysis, and preliminary results suggest that treatment with the drugs reduces LPS-induced NLRP3 inflammasome activation. |
