The activity of the pentose phosphate pathway is increased in response to oxidative stress in Alzheimer's disease

Abstract

In order to assess the integrity of antioxidant enzymes in Alzheimer's disease, the activities of glutathione peroxidase, glutathione reductase and two enzymes of the pentose phosphate pathway (glucose-6-phosphate dehydrogenase and 6-phosphonogluconate dehydrogenase) were determined in three regions of postmortem neocortex of controls and subjects with Alzheimer's disease. The activities of glutathione peroxidase and glutathione reductase were unaffected in Alzheimer's disease. By contrast, there was a selective increase in the activities of glucose-6-phosphate dehydrogenase and 6-phosphonogluconate dehydrogenase in the inferior temporal cortex of Alzheimer subjects. These changes negatively correlated with the Fe2+/ascorbate-induced lipid peroxidation which (in a previous study of the same subjects) was also found to be selectively elevated in the inferior temporal cortex. Increased activity of the pentose phosphate pathway probably occurs in response to increased prooxidant activity since both glucose-6-phosphate and 6-phosphonogluconate inhibited H2O2-induced lipid peroxidation in a concentration dependant fashion (IC50 = 504 +/- 105 microM and 88 +/- 12 microM, respectively). Together, these data suggest that not only is oxidative stress a feature of Alzheimer's disease, but also that it occurs because of increased prooxidant activity rather than a diminished antioxidant capacity.

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

“…Vulnerable neurons may have increased dicarbonyl products and/or decreased turnover of modified proteins (30). These data fit with increased carbonyl reductase, alcohol dehydrogenase (31), and pentose-phosphate pathway activities (32) in brains from AD patients. In addition, recent data stress the potential importance of glyoxalase I, an enzyme against reactive dicarbonyls, as a risk factor in AD pathogenesis (33).…”

Effect of Indigofera tinctoria on ?-amyloid (25-35) mediated Alzheimer’s disease in mice: Relationship to antioxidant activity

“…Elevation of brain oxidative status of amnesic mice resembled the clinical pathology observed in Alzheimer's disease patients (Palmer, 1999). In this experiment condition, the treatment of p amyloid resulted in a significant decrease of glutathione reductase, glutathione peroxidase and SOD activities.…”

Antioxidant effect of phycocyanin on oxidative stress induced with monosodium glutamate in rats

“…Aksenov and Markesbery (2001) studied the increased level of oxidative modifications in proteins, lipids, and nucleic acids in the brain of patients with Alzheimer's disease, and they found that the total thiol content was increased by ~ 20% in the patients with Alzheimer in the cerebellum, indicating that the oxidative agents promoted the damage irreversible in the brain. Other investigators have suggested that the synthesis of SH-containing could be increased as a response to oxidative stress in the brain causing disease, and the antioxidant agents could acted preventing this situation (Palmer, 1999). Corwin and Schwarz (1963) studied the properties of α-tocopherol in the presence of reactive free radicals and found that a tocopherol defense mechanism was involved in the protection of essential sulfhydryl groups since the oxidation of tocopherol in the systems containing sulfhydryl groups protected the cells of oxidative damage.…”