NOS2 and Parkinson disease: This mechanism has been validated in both PD patients and MPTP-induced mouse models-senescent astrocytes in the substantia nigra pars compacta (Snpc) continuously produce high concentrations of iNOS, and the free radicals catalyzed by iNOS can directly penetrate the blood-brain barrier or indirectly trigger programmed death of dopaminergic neurons via oxidative stress [135].