ROLE OF AUTOPHAGY AND THE NRF2/KEAP1 PATHWAY IN THE GLIA DURING OXIDATIVE STRESS IN THE DOSOPHILA BRAIN

Abstract

Excessive levels of reactive oxygen species (ROS) damage cellular components and leads to oxidative stress (Finkel & Holbrook, 2000). Oxidative stress is a major cause of aging, neurodegenerative disease, cardiovascular disease and cancer (Finkel & Holbrook, 2000). Two stress response pathways that help cells cope with oxidative stress are the NRF2/Keap1 pathway, involved in the direct regulation of antioxidants, and the autophagy pathway, the recycling pathway of the cell (Essick & Sam, 2010; Singh et al., 2010). Although autophagy can clean up damage in cells during oxidative stress, it can cause autophagic cell death, especially during highly stressful conditions (Maiuri et al., 2007). In this thesis, the roles of autophagy and the NRF2/Keap1 pathway were examined in the glia during acute oxidative stress, and the role of autophagy was examined during thermal stress and aging. It was hypothesized that down regulation of autophagy and activation of the NRF2/Keap1 pathway in the glia would provide protection of the Drosophila brain from these forms of stress. The results show that down regulation of autophagy provides protection of survival and locomotor ability but there were inconclusive results regarding the protection of dopaminergic neurons after exposure to oxidative stress. Activation of the NRF2/Keap1 Pathway in the glia did not provide any protection to survival or locomotor ability of flies. Furthermore, down regulation of autophagy in the glia did not provide protection from thermal stress nor did it provide extension of the lifespan or delay in age-dependent decline of locomotor ability. In conclusion, only the down regulation of autophagy in the glia provides some protection of the Drosophila brain from oxidative stress.