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Apolipoprotein A-I: Insights from redox proteomics for its role in neurodegeneration.
MedLine Citation:
PMID:  23027708     Owner:  NLM     Status:  Publisher    
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 contributer 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.
Jeriel T R Keeney; Aaron M Swomley; Sarah Förster; Jessica L Harris; Rukhsana Sultana; D Allan Butterfield
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-2
Journal Detail:
Title:  Proteomics. Clinical applications     Volume:  -     ISSN:  1862-8354     ISO Abbreviation:  Proteomics Clin Appl     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101298608     Medline TA:  Proteomics Clin Appl     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Department of Chemistry, Center of Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
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