Affiliations: [a] Department of Chemistry, University of Kentucky, Lexington, KY, USA | [b] Center of Membrane Sciences, University of Kentucky, Lexington, KY, USA | [c] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Correspondence:
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Correspondence to: Prof. D. Allan Butterfield, Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA. Tel.: +1 859 257 3184; Fax: +1 859 257 5876; E-mail: dabcns@uky.edu or Prof. Rukhsana Sultana, Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA. Tel.: +1 859 257 3615; Fax: +1 859 257 5876; E-mail: rsult2@uky.edu.
Abstract: Aging is the major risk factor associated with neurodegenerative diseases, including Alzheimer's disease (AD). Until now no clear understanding of the mechanisms of initiation and progression of this dementing disorder exists. Based on the studies that have been conducted so far amyloid β-peptide (Aβ), a protein found in senile plaques, one of the key pathological hallmarks of AD, has been reported to be critical in the pathogenesis of AD. Studies from our laboratory and others showed that Aβ can induce oxidative stress, which leads to oxidative modification of biomolecules, thereby diminishing the normal functions of neuronal cells and eventually leading to loss of neurons and AD. In this review paper, we summarize evidence of oxidative stress in brains of AD and mild cognitive impairment patients, as well as the results from redox proteomics studies. The investigations have provided insights into the downstream effects of oxidative modification of key brain proteins in the pathogenesis of AD. Based on these redox proteomics results, we suggest future areas of research that could be considered to better understand this devastating dementing disorder.
Keywords: Alzheimer's disease, lipid peroxidation, mild cognitive impairment, oxidative stress, protein carbonylation, protein nitration, redox proteomics
