Metal Dyshomeostasis and Inflammation in Alzheimer’s and Parkinson’s Diseases: Possible Impact of Environmental Exposures

Figure 5

Chemical stress and aging can alter microglia reactivity and activation of the phagocytic NADPH oxidase complex. (a) Stimulation of microglia induces the parallel activation of oxidase components within the cytoplasm. This activation causes the conversion of Rac into an active GTP-bound form and the phosphorylation of p47phox and p67phox. These subunits then translocate to the membrane where they interact with p22phox and gp91phox (NOX) to initiate ROS production (b) [180]. Excessive or prolonged inflammation (e.g., IL-1β, IL-6, TNF-𝛼) (c) and ROS resulting from increased microglial activation may contribute to neuronal damage (d). In addition, chemicals can damage complex I in mitochondria ((e) figure adapted from [181]) and induce deleterious changes to neurons in SN by ROS formation and ATP depletion. The figure is adapted with modifications from [168].