title: Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain.
abstract: Lipid peroxidation involves a cascade of reactions in which production of free radicals occurs selectively in the lipid components of cellular membranes. Polyunsaturated fatty acids easily undergo lipid peroxidation chain reactions, which, in turn, lead to the formation of highly reactive electrophilic aldehydes. Among these, the most abundant aldehydes are 4-hydroxy-2-nonenal (HNE) and malondialdehyde, while acrolein is the most reactive. Proteins are susceptible to posttranslational modifications caused by aldehydes binding covalently to specific amino acid residues, in a process called Michael adduction, and these types of protein adducts, if not efficiently removed, may be, and generally are, dangerous for cellular homeostasis. In the present review, we focused the discussion on the selective proteins that are identified, by redox proteomics, as selective targets of HNE modification during the progression and pathogenesis of Alzheimer disease (AD). By comparing results obtained at different stages of the AD, it may be possible to identify key biochemical pathways involved and ideally identify therapeutic targets to prevent, delay, or treat AD.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA. Electronic address: dabcns@uky.edu.
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism / Q000633:toxicity; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D005231:Fatty Acids, Unsaturated; D011506:Proteins; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal