Organisms have evolved to adapt to toxic levels of free radicals through homeostasis. A variety of both hydrophillic and hydrophobic antioxidant compounds are either generated or extracted by living aerobic organisms. Furthermore, several antioxidant enzymes are synthesized that inactivate reactive oxygen intermediates. The combination of these compounds and enzymes enable animals to survive oxidative stress. Some oxidative damage does still occur, and this damage is removed and repaired by a series of enzymes. Because internal environments are continuously changing, excitation and inhibition of these mechanisms occur by means of negative feedback. (Davies, 1995)
Despite all the systems at work to protect tissue from free radical injury, it is inevitable that oxidative damage will remain permanently. This damage is implicated in several diseases and syndromes, such as cancer, heart disease, strokes, rheumatoid arthritis, lupus, cataracts, Parkinson's disease, Alzheimer's disease, and perhaps the act of aging itself. An abundance of research has been committed to the development of neuroprotectors and the research of environmental factors that help protect organisms from cell death due to oxidative stress. (Davies, 1995)
The way that oxidative stress affects Alzheimer's disease is neurochemically by a transmitter-specific loss of neurons, which extends to several neuronal systems with time. It is theorized that amyloid beta peptides, known as Abeta, increase the activity of free radicals. Abeta is a main constituent of the plaques that are chracteristic in Alzheimer's patients. Abeta is toxic because it generates free radicals that inhibit astrocyte glutamate transporters, leading to the failure to uptake glutamate. This inhibition leads to glutamate-induced cell death. (Butterfield et al, 1996)
In an experiment conducted by Butterfield et al, neurons treated with Abeta (25-35) prevented the uptake of L-glutamate in rat hippocampal astrocye cultures. This effect was prevented by the antioxidant Trolox. This research leads to the conclusion that certain antioxidants decrease the inhibtion of glutamate transporters. In another study by Dargusch et al, clones of a cell line from rats that are resistant to Abeta and high levels of peroxides were created. When treated with Abeta, the parent cells accumulated intracellular hydrogen peroxide while the Abeta resistant cells did not. The absence of peroxide accumulation in the Abeta resistant clones is attributed to the increase of catalase, glutathione peroxidase, and their processes. Nonresistant cells that were injected with these enzymes were also more resistant to Abeta and oxidative damage. This study indicates that increased enzyme activities account for part of their resistance to free oxygen toxicity. (Butterfield et al, 1996)
Currently, this and similar research does not provide a cure for Alzheimer's disease. It is in it's elementary stages. Until it has been applied to living animals, it's usefulness is unknown. Additionally, even if a neuroprotectant, such as Trolox, or a treatment of combative enzymes is perfected and approved as a treatment for Alzheimer's, it cannot reverse damage that has already occurred. It can only prevent further damage due to the pathomechanism of oxidative stress. (Butterfield et al, 1996)