DIMETHYLARGININASE, A NITRIC-OXIDE REGULATORY PROTEIN, IN ALZHEIMER-DISEASE

In this study, we show that dimethylargininase, a zinc protein involve d 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 neur ons in age-matched control cases. Seen in the context of earlier studi es showing widespread nitric oxide related damage in AD and the role o f dimethylargininase to activate nitric oxide synthetase, through cata lytic removal of its endogenous inhibitors, these findings indicate ma jor alterations in nitric oxide regulation in AD. Further, that low le vels of zinc specifically inhibit dimethylargininase may provide a lin k 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 importan t roles in the pathogenesis of AD. (C) 1998 Elsevier Science Inc.