The mechanistic underpinnings of the proportional increase in nuclear AT1 in surviving dopamine neurons in nigrosome 1 of prePD and PD patients might be related to accompanying elevation in nuclear expression of superoxide-generating Nox4, which in turn may explain our finding of increased oxidative damage to DNA as measured by elevated 8-OH guanosine (summarized in Figure 9) and ongoing caspase-3-mediated proteolysis and cell death. The gene discussed is NOX4; the disease is Parkinson disease.