Figure 2.

Taken with some modification from [91] with permission. These four pathways produce both pathophysiological effects and, in the case of one pathway, therapeutic effects. The main effects are produced via elevated calcium signaling, such as those discussed in Figure 1, which disrupts normal synaptogenesis. The peroxynitrite pathway going to the right can cause large elevations of peroxynitrite (ONOO- or ONOO(-)), a potent oxidant which breaks down to release highly reactive free radicals which produce oxidative stress. Peroxynitrite also produces large increases in NF-kappaB and inflammatory cytokines and inflammation. Oxidative stress and inflammation occur in almost all human chronic diseases, including ASDs. The therapeutic pathway occurs when there are only modest increases in [Ca²⁺]i. It produces effects that are almost opposite of the effects produced by the peroxynitrite pathway—these therapeutic effects are mostly produced by raising the levels of Nrf2.