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Amyloid β-peptide (Aβ) is a 42-43 amino acid peptide known to accumulate in Alzheimer's disease (AD) brain. We previously reported that the neurotoxicity caused by Aβ is a result of its associated free radicals, which can play an important role in generating oxidative stress. Aβ(25-35)associated oxidative stress-induced neuronal death in vitro is well established by many laboratories, including ours. However, the oxidative stress-induced by the full-length [Aβ(1-42)] peptide is not well investigated. The protective effect of antioxidant vitamin E in full-length peptide-induced oxidative stress also has not been reported. Here, we report that the increased protein oxidation, reactive oxygen species (ROS) formation, and neurotoxicity induced by Aβ(1-42) in primary rat embryonic hippocampal neuronal culture are prevented by the free radical scavenger and anti

According to the free radical theory of aging, reactive oxygen species cause oxidative damage, proposed to be an underlying factor of the aging process. In the current study, we have used electron paramagnetic resonance spin labeling, measurements of protein carbonyl content, an index of protein oxidation, and determination of the activity of glutamine synthetase (an oxidatively sensitive enzyme) to report that cortical synaptosomal membranes from the senescence accelerated-prone (SAMP8) mouse showed structural characteristics of free radical oxidative stress relative to the senescence accelerated-resistant (SAMR1) mouse. The SAMP8 mouse exhibited a decrease in the relevant EPR parameter consistent with oxidative stress (P < 0.002), a decreased glutamine synthetase activity (P < 0.05), and an increased protein carbonyl content (P < 0.01) compared with these parameters in the SAMR1 mouse. Further, because free radical trapping compounds have been demonstrated to extend maximum life span and improve cognition in SAMP8 mice, we investigated the protective nature of the known free radical scavenger, N-tert-butyl-␣-phenylnitrone (PBN), on the physical state of cortical synaptosomal membrane proteins. For 14 days, SAMR1 and SAMP8 mice were injected with 30 mg͞kg PBN while the controls were injected with the corresponding volume of saline. Characteristic of less oxidized systems, cortical synaptosomal membranes from the PBNinjected SAMP8 mouse exhibited a return toward normal values of the relevant EPR parameter [the M I ‫؍‬ ؉1 low-field weakly immobilized line͞M I ‫؍‬ ؉1 low-field strongly immobilized line (W͞S) ratio of a protein-specific spin label] (P < 0.001) compared with that from saline-injected SAMP8 mice. In SAMR1 mice, in contrast to SAMP8, there was no significant change in the conformation of membrane proteins or protein carbonyl content of cortical synaptosomal membranes from the PBN-injected and saline-injected SAMR1 mice, showing that PBN itself did not induce conformational changes in cortical synaptosomal membrane proteins. The results are discussed with reference to the use of free radical scavengers as potential anti-aging agents.Aging and age-related neurological disorders, especially Alzheimer disease and stroke, affect millions of people worldwide. Many hypotheses have been developed to explain aging and age-related neurodegenerative disorders. One of the most compelling, and one for which our laboratory has contributed extensively, is the role of free radical-induced oxidative stress in aging, stroke, Alzheimer disease, Parkinson disease, and Huntington disease (1-20). The free radical theory of normal aging proposes that the slow generation of oxygen free radicals, an unavoidable consequence of life in an aerobic environment, results in cumulative damage to critical cellular components, and eventually leads to age-related pathology (21). A consensus is emerging that free radical processes do play an important role in the etiology of many age-related disorders (10,11,16,17,22,23), althou...