Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease

Vittorio Calabrese, Rukhsana Sultana, Giovanni Scapagnini, Eleonora Guagliano, Maria Sapienza, Rita Bella, Jaroslaw Kanski, Giovanni Pennisi, Cesare Mancuso, Anna Maria Giuffrida Stella, D. A. Butterfield

Research output: Contribution to journalArticlepeer-review

211 Scopus citations

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and memory decline, personality changes, and synapse loss. Increasing evidence indicates that factors such as oxidative and nitrosative stress, glutathione depletion, and impaired protein metabolism can interact in a vicious cycle, which is central to AD pathogenesis. In the present study, we demonstrate that brains of AD patients undergo oxidative changes classically associated with a strong induction of the so-called vitagenes, including the heat shock proteins (HSPs) heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase (TRXr). In inferior parietal brain of AD patients, a significant increase in the expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased, compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was decreased in AD patients, compared with the control group, and was associated with a significant increase in oxidative stress markers (i.e., GSSG, hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes, we observed an increased expression of inducible nitric oxide synthase, HO-1, Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the pathogenesis of AD and indicate that the stress-responsive genes, such as HO-1 and TRXr, may represent important targets for novel cytoprotective strategies.

Original languageEnglish
Pages (from-to)1975-1986
Number of pages12
JournalAntioxidants and Redox Signaling
Volume8
Issue number11-12
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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