These results suggest that PON2 is a major intracellular factor that interacts with estradiol to exert protection to central nervous system cells against oxidative stress and such protection is lower in males due to the lower levels of PON2 expression in brain regions, which may lead to higher susceptibility to neurotoxicity and, therefore, to neurodegenerative diseases. The gene discussed is PON2; the disease is neurodegenerative disease.