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Glutathionylation of the Pro-apoptotic Protein p53 in Alzheimer’s Disease Brain: Implications for AD Pathogenesis

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An Erratum to this article was published on 19 March 2009

Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. The exact mechanism for the AD pathogenesis is not clearly understood. However, a number of hypotheses have been proposed to explain the pathogenesis of AD. One the hypotheses is the oxidative stress hypothesis that is supported by a number of studies which reported an increase in the levels of reactive oxygen/reactive nitrogen species and their products with a concomitant decrease in the levels of antioxidant enzymes in AD brain. In the present study, we measured in AD brain the expression levels of different forms (monomer, dimer and tetramer) of the pro-apoptotic protein, p53, and observed greater levels of p53 monomer and dimer in AD brain compared to control. In addition, we also showed the selective glutathionylation of monomeric and dimeric form of p53 in AD brain. We propose that glutathionylation of p53 may prevent the formation of tetramer, an aggregate form required for effective action of p53, and may be involved in oxidative stress conditions and neurodegeneration observed in this dementing disorder.

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Acknowledgments

This research was supported in part by NIH grants to D.A.B. [AG-05119;AG-10836; AG-029839]. We thank the faculty of the UK ADC Neuropathology Core for providing the AD and control brain specimens used in this study.

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Authors and Affiliations

  1. Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40506-0055, USA

    Fabio Di Domenico, Giovanna Cenini, Rukhsana Sultana, Marzia Perluigi & D. Allan Butterfield

  2. Department of Biomedical Sciences and Biotechnologies, University of Brescia, Viale Europa 11, 25124, Brescia, Italy

    Giovanna Cenini, Daniela Uberti & Maurizio Memo

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

    Fabio Di Domenico & Marzia Perluigi

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  1. Fabio Di Domenico
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  2. Giovanna Cenini
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  3. Rukhsana Sultana
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  4. Marzia Perluigi
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  7. D. Allan Butterfield
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Correspondence to D. Allan Butterfield.

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Special issue article in Honour of Dr. Akitane Mori.

Fabio Di Domenico and Giovanna Cenini contributed equally.

An erratum to this article can be found at http://dx.doi.org/10.1007/s11064-009-9955-2

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Domenico, F.D., Cenini, G., Sultana, R. et al. Glutathionylation of the Pro-apoptotic Protein p53 in Alzheimer’s Disease Brain: Implications for AD Pathogenesis. Neurochem Res 34, 727–733 (2009). https://doi.org/10.1007/s11064-009-9924-9

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