Oxidatively modified,mitochondria-relevant brain proteins in subjects with Alzheimer disease and mild cognitive impairment |
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Authors: | Rukhsana Sultana D Allan Butterfield |
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Institution: | (1) Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506-0055, USA;(2) Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA;(3) Department of Biochemical Sciences, University of Rome “La Sapienza”, Rome, 00185, Italy; |
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Abstract: | Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized histopathologically by the presence of
senile plaques (SP), neurofibrillary tangles and synapse loss in selected brain regions. Positron emission tomography (PET)
studies of glucose metabolism revealed decreased energetics in brain of subjects with AD and arguably its earliest form, mild
cognitive impairment (MCI), and this decrease correlated with brain structural studies using MRI. The main component of senile
plaques is amyloid beta-peptide (Aβ), a 40–42 amino acid peptide that as oligomers is capable of inducing oxidative stress
under both in vitro and in vivo conditions and is neurotoxic. In the mitochondria isolated from AD brain, Aβ oligomers that
correlated with the reported increased oxidative stress markers in AD have been reported. The markers of oxidative stress
have been localized in the brain regions of AD and MCI that show pathological hallmarks of this disease, suggesting the possible
role of Aβ in the initiation of the free-radical mediated process and consequently to the build up oxidative stress and AD
pathogenesis. Using redox proteomics our laboratory found a number of oxidatively modified brain proteins that are directly
in or are associated with the mitochondrial proteome, consistent with a possible involvement of the mitochondrial targeted
oxidatively modified proteins in AD progression or pathogenesis. The precise mechanistic link between mitochondrial oxidative
damage and role of oligomeric Aβ has not been explicated. In this review, we discuss the role of the oxidation of mitochondria-relevant
brain proteins to the pathogenesis and progression of AD. |
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