| Abstract | The presence of Reactive Oxidative Species (ROS) in the brain have been linked to the etiology of Alzheimer's disease and neurodegeneration. In this project, novel antioxidant Indole derivative drugs were tested on BV-2 microglial cells using RT-qPCR to assess their ability to activate antioxidant gene expression. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a gene transcription factor that is activated by oxidative stress and binds to a sequence called the Antioxidant Response Element (ARE), a region upstream of the DNA promoter sequence. Nrf2 activates transcription of antioxidative genes. Based on theoretical docking studies, we hypothesize that the novel compounds will disrupt the interaction between Nrf2 and its inhibitor KEAP, releasing Nrf-2 and enabling it to translocate to the nucleus. The novel antioxidant drugs should either increase the transcription of Nrf2-activated genes or reduce overall levels of antioxidative stress within cells. We tested for antioxidant properties by measuring Hemeoxygenase-1 (HO-1) and Nrf2 mRNA levels in BV-2 cells in the presence of these compounds. |
