Oxidative and nitrosative modifications of biliverdin reductase-a in the brain of subjects with alzheimer's disease and amnestic mild cognitive impairment

Eugenio Barone, Fabio Di Domenico, Giovanna Cenini, Rukhsana Sultana, Raffaella Coccia, Paolo Preziosi, Marzia Perluigi, Cesare Mancuso, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Biliverdin reductase-A (BVR-A) is a pleiotropic enzyme and plays pivotal role in the antioxidant defense against free radicals as well as in cell homeostasis. Together with heme oxygenase, BVR-A forms a powerful system involved in the cell stress response during neurodegenerative disorders including Alzheimer's disease (AD), whereas due to the serine/threonine/tyrosine kinase activity the enzyme regulates glucose metabolism and cell proliferation. In this paper, we report results that demonstrate BVR-A undergoes post-translational oxidative and nitrosative modifications in the hippocampus, but not cerebellum, of subjects with AD and amnestic mild cognitive impairment (MCI). A significant increase of nitrated BVR-A was demonstrated only in AD and MCI hippocampi, whereas no significant modifications were found in cerebellar tissue. In addition, a significant reduction in protein carbonyl-derivatives of BVR-A was found in both AD and MCI hippocampi (15% and 18%, respectively). Biliverdin reductase-bound 4-hydroxynonenals were not modified in hippocampi and cerebella from AD and MCI subjects. These results supported the hypothesis of a prevalence of nitrosative stress-induced modifications on BVR-A structure, and this evidence was confirmed by a significant upregulation of inducible nitric oxide synthase in hippocampal tissue of subjects with AD and MCI that was not present in cerebellum. In conclusion, nitrosative stress-induced modifications on hippocampal BVR-A are an early event in the pathogenesis of AD since they appear also in MCI subjects and could contribute to the antioxidant and metabolic derangement characteristic of these neurodegenerative disorders.

Original languageEnglish
Pages (from-to)623-633
Number of pages11
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2011


  • Alzheimer's disease
  • biliverdin reductase
  • heme oxygenase
  • mild cognitive impairment
  • neurodegenerative disorders
  • oxidative stress

ASJC Scopus subject areas

  • Neuroscience (all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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