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Quantitative proteomic analysis of differentially expressed proteins in Aβ(17-42) treated synaptosomes

Jaffer Mohammed1, Joseph T. Johnson, Rukhsana Sultana, Joshua B. Owen, Tanea T. Reed


Oxidative stress has been associated in the pathogenesis of numerous diseases such as various neurodegenerative disorders, ischemia, and cancer. The brain is susceptible to oxidative stress due to its high content of peroxidizable unsaturated fatty acids, high consumption of oxygen, and elevated levels of free radicals. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can react with biomolecules such as proteins, lipids, carbohydrates, DNA, and RNA, which can lead to oxidative damage, cellular dysfunction, and ultimately cell death. Down syndrome (DS) is caused by trisomy of chromosome 21, a genetic abnormality in which an extra copy of the chromosome is present. DS patients have extensive deposition of Aβ(17-42) peptide, which could contribute to their increased rate of developing Alzheimer’s disease (AD), which is consistent with current research. Since AD cannot be properly diagnosed until autopsy, development of a novel Down syndrome model using Aβ(17-42) could be beneficial in determining oxidative stress levels and their relationship to mild cognitive impairment (MCI), the earliest form of AD. This work will demonstrate the use of a novel Down Syndrome model and its correlation to oxidative stress. We have found a significant difference between oxidative stress levels in Aβ(17-42) treated synaptosomes and control. By using proteomics, we have also identified several biomarkers including aldehyde dehydrogenase, aldolase, α-enolase, heat shock cognate 71, peptidyl-prolyl cis-trans isomerase, and ATP synthase α chain. Our present findings suggest the role of Aβ(17-42) as one of the contributing factors in mediating oxidative stress in DS and AD brain leading to neurodegeneration. This novel DS model may have potential applications as a diagnostic tool to identify biomarkers that may contribute to Alzheimer’s disease.

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