Can enzyme kinetics of prooxidants teach us a lesson about the treatment of Alzheimer's disease: a pilot post-mortem study.

AbstractObjectives. Oxidative stress (OS), is defined as an imbalance of pro- and antioxidants, leading to increased production of free radicals, which can lead to cell damage and death, has been postulated as important factors in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Most research has concentrated on the antioxidant system, for the first time, this proof of concept study examines the prooxidant system by investigating kinetic parameters of the free radical producing enzyme xanthine oxidase directly in post mortem brain tissue. Methods. We determined the Michaelis–Menten constant (KM) and the maximal velocity (VMax) of xanthine oxidase (XO) in the cortico-limbic system of patients with AD using activity assays. Results. We found the Michaelis–Menton constant of XO significantly decreased in hippocampus of patients with AD compared to controls. None of the other brain regions showed any significant alterations of these parameters. Conclusions. These results add f...