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We aim to understand the molecular mechanisms involved in age-related progressive neurodegenerative diseases. Our primary focus is on the innate immune responses by glia and their effect on neuronal health. We investigate how these cells respond to chemokines,cytokines, and misfolded proteins; deciphering specific signaling pathways. Although the cause of many sporadic neurodegenerative disorders like Parkinson's disease (PD) are unknown, it is hypothesized that genetic vulnerability and environmental factors are important. We are currently following several lines of investigation including the role of increased oxidative stress, protein misfolding and inflammation on neurodegeneration using mouse and cell culture models. We have shown that one protein known to be involved in PD, alpha-synuclein, can increase oxidative stress, proinflammatory molecules and alter neuronal membrane conductance giving us a clue that these molecular events are important in the pathogenesis of PD.