Proteomic identification of nitrated proteins in Alzheimer's disease brain

Alessandra Castegna, Visith Thongboonkerd, Jon B. Klein, Bert Lynn, William R. Markesberyl, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

503 Scopus citations


Nitration of tyrosine in biological conditions represents a pathological event that is associated with several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). Increased levels of nitrated proteins have been reported in AD brain and CSF, demonstrating the potential involvement of reactive nitrogen species (RNS) in neurodegeneration associated with this disease. Reaction of NO with O2-. leads to formation of peroxynitrite ONOO-, which following protonation, generates cytotoxic species that oxidize and nitrate proteins. Several findings suggest an important role of protein nitration in modulating the activity of key enzymes in neurodegenerative disorders, although extensive studies on specific targets of protein nitration in disease are still missing. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. We previously applied a proteomics approach to determine specific targets of protein oxidation in AD brain, by successfully coupling immunochemical detection of protein carbonyls with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry analysis. In the present study, we extend our investigation of protein oxidative modification in AD brain to targets of protein nitration. The identification of six targets of protein nitration in AD brain provides evidence to the importance of oxidative stress in the progression of this dementing disease and potentially establishes a link between RNS-related protein modification and neurodegeneration.

Original languageEnglish
Pages (from-to)1394-1401
Number of pages8
JournalJournal of Neurochemistry
Issue number6
StatePublished - Jun 2003


  • 3-Nitrotyrosine
  • Alzheimer's disease
  • Neurodegeneration
  • Proteomics
  • Reactive nitrogen species

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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