Dimethylargininase, a nitric oxide regulatory protein, in Alzheimer disease.

In this study, we show that dimethylargininase, a zinc protein involved in the regulation of nitric oxide synthase, is specifically elevated in neurons displaying cytoskeletal abnormalities and oxidative stress in Alzheimer disease (AD) while none of this enzyme was found in neurons in age-matched control cases. Seen in the context of earlier studies showing widespread nitric oxide related damage in AD and the role of dimethylargininase to activate nitric oxide synthetase, through catalytic removal of its endogenous inhibitors, these findings indicate major alterations in nitric oxide regulation in AD. Further, that low levels of zinc specifically inhibit dimethylargininase may provide a link between the numerous studies showing specific abnormalities in zinc and oxidative stress. Finally, our results provide additional evidence that oxidative stress- and nitric oxide-mediated events play important roles in the pathogenesis of AD.