Our laboratory investigates molecular mechanisms underlying neurodegeneration associated with neuroinflammation during HIV infection. As inflammation and oxidative stress play prominent roles in progression of non-infectious neurodegenerative diseases such as Alzheimer disease (AD) and Parkinson disease (PD), we often extend our findings in HIV associated neurocognitive dysfunction (HAND) to these diseases in the hopes of uncovering common mechanism and thereby, common therapeutic targets. We are interested in understanding how neuroinflammation induces neuroprotective and neurotoxic responses in glia (astrocytes and microglia). Further, we are interested in how neurons interpret these extracellular cues and how this causes neuronal dysfunction, neuritic damage and neuronal loss. Currently we are focusing our research efforts on the role of cell cycle proteins, the endogenous antioxidant response and unfolded protein response in HAND. Thus far, our studies indicate that three cell cycle proteins, retinoblastoma (pRb), E2F1 transcription factor, and mouse double minute x (MDMx) play novel roles in neuronal survival and death. In parallel, HIV-induced neuroinflammation induces activation of the unfolded protein response in neurons, astrocytes, and macrophages. By assessing the interaction of these three convergent pathways in neurons, astrocytes and microglia responding to neuroinflammation, we hope to gain a greater understanding of the basic mechanisms underlying neuronal damage, dysfunction and in HAND and identify drugable targets for treatment of this and other neurodegenerative diseases.