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

Abstract

Objectives. 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 (K_M) and the maximal velocity (V_Max) 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 further evidence to the amount of research indicating that OS plays an important role in AD. Moreover, these results should encourage more research in this field and it maybe speculated that this might open new avenues for treatment and prevention in AD.

Key words::

• Hippocampus
• Alzheimer's disease
• post-mortem
• oxidative stress
• xanthine oxidase

Acknowledgements

We thank Tonka Gregorieva Frentzel, RWHT Aachen University, for her excellent technical support.

Statement of interest

Prof. F. Schneider has received funding from AstraZeneca and Jansen Cilag and was on the advisory board for AstraZeneca until 2008.