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Oxidatively modified proteins in Alzheimer’s disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis

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Abstract

Oxidative stress has been implicated in the pathogenesis of a number of diseases including Alzheimer’s disease (AD). The oxidative stress hypothesis of AD pathogenesis, in part, is based on β-amyloid peptide (Aβ)-induced oxidative stress in both in vitro and in vivo studies. Oxidative modification of the protein may induce structural changes in a protein that might lead to its functional impairment. A number of oxidatively modified brain proteins were identified using redox proteomics in AD, mild cognitive impairment (MCI) and Aβ models of AD, which support a role of Aβ in the alteration of a number of biochemical and cellular processes such as energy metabolism, protein degradation, synaptic function, neuritic growth, neurotransmission, cellular defense system, long term potentiation involved in formation of memory, etc. All the redox proteomics-identified brain proteins fit well with the appearance of the three histopathological hallmarks of AD, i.e., synapse loss, amyloid plaque formation and neurofibrillary tangle formation and suggest a direct or indirect association of the identified proteins with the pathological and/or biochemical alterations in AD. Further, Aβ models of AD strongly support the notion that oxidative stress induced by Aβ may be a driving force in AD pathogenesis. Studies conducted on arguably the earliest stage of AD, MCI, may elucidate the mechanism(s) leading to AD pathogenesis by identifying early markers of the disease, and to develop therapeutic strategies to slow or prevent the progression of AD. In this review, we summarized our findings of redox proteomics identified oxidatively modified proteins in AD, MCI and AD models.

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Acknowledgments

This work was supported in part by grants from NIH to D.A.B. [AG-05119; AG-10836; AG-029839].

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Authors and Affiliations

  1. Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY, 40506-0055, USA

    Rukhsana Sultana & D. Allan Butterfield

  2. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Rukhsana Sultana & D. Allan Butterfield

  3. Department of Biochemical Sciences, University of Rome “La Sapienza”, Rome, 00185, Italy

    Marzia Perluigi

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  1. Rukhsana Sultana
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  2. Marzia Perluigi
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  3. D. Allan Butterfield
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Correspondence to D. Allan Butterfield.

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Sultana, R., Perluigi, M. & Butterfield, D.A. Oxidatively modified proteins in Alzheimer’s disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis. Acta Neuropathol 118, 131–150 (2009). https://doi.org/10.1007/s00401-009-0517-0

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  • DOI: https://doi.org/10.1007/s00401-009-0517-0

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