Oxidative stress in Alzheimer's disease brain: New insights from redox proteomics

Alzheimer's disease, an age-related neurodegenerative disorder, is characterized clinically by a progressive loss of memory and cognitive functions. Neuropathologically, Alzheimer's disease is defined by the accumulation of extracellular amyloid protein deposited senile plaques and intracellular neurofibrillary tangles made of abnormal and hyperphosphorylated tau protein, regionalized neuronal death, and loss of synaptic connections within selective brain regions. Evidence has suggested a critical role for amyloid-beta peptide metabolism and oxidative stress in Alzheimer's disease pathogenesis and progression. Among the other indices of oxidative stress in Alzheimer's disease brain are protein carbonyls and 3-nitrotyrosine, which are the markers of protein oxidation. Thus, in this review, we discuss the application of redox proteomics for the identification of oxidatively modified proteins in Alzheimer's disease brain and also discuss the functions associated with the identified oxidized proteins in relation to Alzheimer's disease pathology. The information obtained from proteomics may be helpful in understanding the molecular mechanisms involved in the development and progression of Alzheimer's disease as well as of other neurodegenerative disorders. Further, redox proteomics may provide potential targets for drug therapy in Alzheimer's disease. (c) 2006 Elsevier B.V. All rights reserved.