title: Glutathionylation of the pro-apoptotic protein p53 in Alzheimer's disease brain: implications for AD pathogenesis.
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.
authors.affiliation: Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Domenico
authors.forename: Fabio
authors.initials: F
authors.lastname: D Domenico
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cenini
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Daniela
authors.initials: D
authors.lastname: Uberti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D010296:Parietal Lobe / Q000378:metabolism; D055503:Protein Multimerization; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D005978:Glutathione