Dr. Maguire-Zeiss' laboratory at Georgtown University aims to understand the molecular mechanisms involved in progressive neurodegenerative diseases like Parkinson's disease and HAND. The laboratory focuses on glial-directed innate immune responses and the effect of inflammation on neuronal health and function. By investigating how glial cells respond to chemokines/cytokines and misfolded proteins, specific signaling pathways are identified and novel therapeutics are subsequently identified and tested. For example, the Maguire-Zeiss lab demonstrated that the Parkinson's disease relevant protein, misfolded alpha-synuclein, increases oxidative stress and alters neuronal membrane conductance. This group also demonstrated that this pathologic protein directly interacts with toll-like receptors on microglia inciting a proinflammatory response in these cells. Importantly, toll-like receptor antagonists attenuate this inflammatory response. Using primary cultures, acute brain slices, and mouse models the Maguire-Zeiss lab is helping to decipher the molecular events important for the pathogenesis of disorders like Parkinson's disease and HAND in an effort to discover novel therapeutic approaches for these debilitating diseases.