Free radical oxidative stress is a hallmark of aging and age-related neurodegenerative disorders such as Alzheimer's disease (AD). Such oxidative stress is manifested in neurons by protein oxidation, lipid peroxidation, reactive ox ygen species (ROS) production, mitochondrial dysfunction, and functional impairment of key transmembrane transport proteins, among many others. Our laboratory studies these and other aspects of oxidative stress in brain membranes using a va riety of techniques, including magnetic resonance (both EPR and NMR), fluorescence, chemiluminescence, Western blotting, HPLC analysis, enzyme kinetics, etc. Our group has described how oxidative stress associated with amyloid b-peptide, a 42-amino acid peptide deposited in AD brains, leads to neurotoxicity and how various antioxidants can modulate or prevent this oxidative stress and neuronal death. For example, the figure, illustrating result s from confocal laser fluorescence microscopy, shows how Ab leads to ROS formation in neurons, but the free radical antioxidant vitamin E markedly inhibits this oxidation. Insight into the molecular basis for and potential therapeutic interventions in aging and age-related neurodegenerative disorders is envisaged from our research.

Our laboratory is the first to use proteomics to identify oxidatively modified brain proteins in subjects with AD and, arguably, its earliest form, mild cognitive impairment (MCI). Proteins identified have provided new insights into molecular processes involved in mechanisms of neuronal death in and progression of AD.

Ab(1-42) Added to Neurons Induces ROS That Are Blocked by Vitamin E

Processes involved in redox proteomics, which is used to identify oxidatively modified brain proteins in Alzheimer's disease and other neurodegenerative disorders.