Inflammatory Mechanisms of Neurodegeneration in Toxin-Based Models of Parkinson's Disease

Figure 1

Conceptual overview of how environmental toxins may provoke DA neurodegeneration in Parkinson’s disease and its animal models. Chronically activated microglia are integral mediators of pathology, synthesizing and secreting a plethora of prooxidant and proinflammatory factors, several of which (e.g., IFN-γ, PGs) may form positive feedback loops to stimulate the production of further inflammatory/oxidative factors (e.g., ROS, PGs) by microglial cells. Several mutually nonexclusive mechanisms exist whereby toxin-induced microglial release of prooxidant/inflammatory agents may lead to DA neurodegeneration; these include lipid peroxidation, DNA damage and the activation of intracellular apoptotic pathways. Additionally, there is evidence to suggest that both adaptive immune responses (e.g., T cell-dependent) and cell-autonomous oxidative processes (e.g., DA-quinone formation) may contribute to DA neuronal loss in PD.