The etiology of neurodegenerative disorders is multifactorial and consists of an interaction between aging, environmental factors, and genetic predisposition. Neuronal cell loss in specific regions of the central nervous system and the resulting clinical symptoms are used to characterize different neurological syndromes. While the selectivity of neuronal cell death is not clearly understood, it is in part attributed to the physiological role and microenvironment of the impacted cells. In this review, innate immune responses in the central nervous system are described. Chronic upregulation of this pathway, orchestrated mainly by microglial cells, may jeopardize neuronal integrity through the prolonged production of toxic inflammatory mediators. Environmental exposures that further enhance the innate immune response may accelerate microglia-driven neurodegeneration. Environmental factors that can trigger inflammatory events in the central nervous system are lipopolysaccharide, aluminum, and particulate matter present in air pollution. These factors may enhance existing age-related inflammation in the central nervous system and thus accelerate neuronal toxicity.