Disease progression from AMC → prePD → PD was also associated with increases in Nox4, oxidative damage to DNA, and activation of caspase-3 in the nuclei of dopamine neurons, giving support to the idea that an AngII/AT1/Nox4-superoxide axis contributes to the neurooxidative injury in dopamine neurons and underscoring the need for further studies of modifiers of the brain RAS activity for preventive and/or symptomatic treatment of neurodegenerative diseases. This evidence concerns the gene AGT and neurodegenerative disease.