Figure 1. Neurotoxic effects of oxidative stress.

Neurotoxicity may occur through an elevation of superoxide anion (O₂^•−) by mitochondria, by autoxidation of neurotransmitters such as Dopamine (DA), or by inappropriately activated microglia, any or all of which may result in increased H₂O₂ levels, increased formation of the highly reactive hydroxyl radical (HO^•) and superoxide (O₂^•−). Phospholipids and proteins, sugars, RNA and DNA are all susceptible to damage by HO^• as are cell membranes, and both nuclear and mitochondrial chromosomes. These factors closely link hypotheses involving mitochondrial dysfunction, neuro-inflammation, oxidative stress, and the essential role of Nrf2 in protein degradation, through activation of the 20S Proteasome that selectively degrades oxidized proteins, and modulating macrophage activation in response to neuro-inflammation.