title: Apolipoprotein A-I: insights from redox proteomics for its role in neurodegeneration.
abstract: Proteomics has a wide range of applications, including determination of differences in the proteome in terms of expression and post-translational protein modifications. Redox proteomics allows the identification of specific targets of protein oxidation in a biological sample. Using proteomic techniques, apolipoprotein A-I (ApoA-I) has been found at decreased levels in subjects with a variety of neurodegenerative disorders including in the serum and cerebrospinal fluid (CSF) of Alzheimer disease (AD), Parkinson disease (PD), and Down syndrome (DS) with gout subjects. ApoA-I plays roles in cholesterol transport and regulation of inflammation. Redox proteomics further showed ApoA-I to be highly oxidatively modified and particularly susceptible to modification by 4-hydroxy-2-trans-nonenal (HNE), a lipid peroxidation product. In the current review, we discuss the consequences of oxidation of ApoA-I in terms of neurodegeneration. ROS-associated chemotherapy related ApoA-I oxidation leads to elevation of peripheral levels of tumor necrosis factor-α (TNF-α) that can cross the blood-brain barrier (BBB) causing a signaling cascade that can contribute to neuronal death, likely a contributor to what patients refer to as "chemobrain." Current evidence suggests ApoA-I to be a promising diagnostic marker as well as a potential target for therapeutic strategies in these neurodegenerative disorders.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Jeriel T R
authors.initials: JT
authors.lastname: Keeney
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Swomley
authors.forename: Sarah
authors.initials: S
authors.lastname: Förster
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Harris
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D010084:Oxidation-Reduction; D040901:Proteomics
chemical_list: D001053:Apolipoproteins; D015415:Biomarkers