Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death.

Oxidative stress: Free radical production in neural degeneration

Are reactive oxygen species involved in Alzheimer's disease?

Lipid peroxidation (LPO) is a free radical-related process that in biologic systems may occur under enzymatic control, e.g., for the generation of lipid-derived inflammatory mediators, or nonenzymatically. This latter form is associated mostly with cellular damage as a result of oxidative stress, which also involves cellular antioxidants in this process. This article focuses on the relevance of two LPO products, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), to the pathophysiology of human disease. The former has been studied in human serum samples of hepatitis C virus-infected adults and human immunodeficiency virus-infected children. In these two cases it is shown that the specific assay of serum MDA is useful for the clinical management of these patients. The presence of MDA in subretinal fluid of patients with retinal detachment suggests the involvement of oxidative stress in this process. Moreover, we were able to report the dependence of this involvement on the degree of myopia in these patients. The assay of MDA contents in the peripheral nerves of rats fed a chronic alcohol-containing diet or diabetic mice also confirms the pathophysiologic role of oxidative stress in these experimental models. In these two cases, associated with an increase in tissue LPO products content, we detected a decrease of glutathione peroxidase (GSHPx) activity in peripheral nerve, among other modifications. We have demonstrated that in vitro HNE is able to inhibit GSHPx activity in an apparent competitive manner, and that glutathione may partially protect and/or prevent this inactivation. The accumulation of LPO products in the brain of patients with Alzheimer's disease has also been described, and it is on the basis of this observation that we have tried to elucidate the role of oxidative stress and cellular antioxidants in beta-amyloid-induced apoptotic cell death of rat embryo neurons. Finally, we discuss the possible role of the observed vascular effects of HNE on human arteries.

Lipid peroxidation products and antioxidants in human disease.

Age- and peroxidative stress-related modifications of the cerebral enzymatic activities linked to mitochondria and the glutathione system

The formation of thiobarbituric-acid-reactive substances (TBARS) indicative of oxygen-induced lipid peroxidation in vitro was assayed in the frontal cortex, hippocampus, putamen, basal nucleus of Meyn

E. Hauer

Papers

Susceptibility of Brains from Patients with Alzheimer's Disease to Oxygen-Stimulated Lipid Peroxidation and Differential Scanning Calorimetry

Susceptibility of brains from patients with Alzheimer's disease to oxygen-stimulated lipid peroxidation and differential scanning calorimetry