These results were independently conf irmed by analysis of multiple samples of tissue from the same patient and also with brain tissue from a second patient carrying the same mutation.B, was subjected to proteolytic digestion with PK for min under the conditions indicated below each lane.The arrowhead indicates the position of a relatively resistant fragment generated upon PK digestion. The numbers on the right are the molecular weight markers.Five percent homogenates were prepared from frozen brain tissue removed at autopsy from a neurologically normal individual and a GSS case containing the AV mutation.The left panel shows a portion of each sample before digestion with PK and the right panel after the digestions.N ormal G S S N ormal G S S M M H H M H H C J D WT: rectly or indirectly, neurodegeneration.There are three lines of evidence for thefirst step.The proteolysis reactions were terminated by adding PMSF to mM, incubating an additional min, and transferring the sample to volumes of boiling SDS and. Serban for reagents; G.Supported by NIH grant AG and the Medical Scientist Training Program.z FEBRUARY zwww.sciencemag.org The user has requested enhancement of the downloaded file.NATURAL ANTIOXIDANTS AND NEURODEGENERATIVE DISEASES S.Although protein aggregation plays a pivotal role in both AD and PD, there is increasing evidence that excessive accumulation of reactive oxygen species that occurs during normal and pathological brain aging contributes to neuronal losses and dysfunction.Based on these observations, it has been hypothesized that natural antioxidants derived from food, beverages and natural extracts may be beneficial to prevent or delay the occurrence of agerelated cognitive deficits and neurodegenerative diseases.We will summarize in this review the role of oxidative stress in pathological brain aging, and provide evidence for a role for antioxidant molecules as therapeutic agents.Postmortem analyses of AD and PD brains have demonstrated evidence of oxidative stress including elevated levels of products of lipid peroxidation and DNA alterations.In support of this hypothesis, an epidemiological study performed in elderly subjects reported that fruit and vegetablederived flavonoid intake was inversely correlated with the risk of dementia, with a relative risk, followed by vegetables, wine and tea. Moreover, another study suggested that dietary antioxidant flavonoids in a cohort of men aged to years who demonstrated that persons in the top quintile of fruit and vegetable intake relative to persons in the bottom quintile, particularly for citrus fruit. reasch Carbamazepine Recent reports suggested that daily consumption of glasses of red wine may be linked to lower risks of AD, cognitive impairment and macular degeneration, in particular in elderly individuals without the APOE epsilon allele. Other studies reported that a moderate consumption of alcohol ameliorated cognitive performance, relative to elderly that do not consume alcohol.Clinical evidence supporting a beneficial role for various kinds of tea is still rather limited.This discrepancy may be due to confounding factors and controlled clinical trials will be required to confirm the effectiveness of vitamins E and C supplementation in the prevention of stroke.In support of this hypothesis, we have reported that the flavonoid fraction may account, at least in part, for the protective effects of the total extract against toxicity induced bybamyloid in hippocampal cells is an amino acid derived from carnitine that possesses several properties including antioxidant activities and enhancing mitochondrial function.