Apolipoprotein A-I: Insights from redox proteomics for its role in neurodegeneration

Authors

  • Jeriel T. R. Keeney,

    1. Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
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  • Aaron M. Swomley,

    1. Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
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  • Sarah Förster,

    1. Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
    2. Department of Biochemistry, Institute of Animal Sciences, University of Bonn, Bonn, Germany
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  • Jessica L. Harris,

    1. Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
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  • Rukhsana Sultana,

    1. Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
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  • D. Allan Butterfield

    Corresponding author
    • Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
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  • Colour Online: See the article online to view Figs. 1 and 2 in colour.

Correspondence: Professor D. Allan Butterfield, Department of Chemistry, Center of Membrane Science, and Sanders Brown Center on Aging, 249 Chemistry-Physics Building, University of Kentucky, Lexington, KY 40506, USA

E-mail: dabcns@uky.edu

Fax: +1-859-323-1464

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.

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