Oxidative stress and neurodegeneration

Paula I. Moreira, Mark A. Smith, Xiongwei Zhu, Akihiko Nunomura, Rudy J. Castellani, George Perry*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

Oxidative stress is a well-studied early response in chronic neurodegenerative diseases, including Alzheimer's disease, where neuronal loss can exceed 90% in the vulnerable neuronal population. Oxidative stress affects all classes of macromolecules (sugar, lipids, proteins, and DNA), leading inevitably to neuronal dysfunction. We observed that Nε- (carboxymethyl)lysine (CML), the predominant advanced glycation end product that accumulates in vivo, along with its glycation-specific precursor hexitol-lysine, are increased in neurons from cases of Alzheimer's disease, especially those containing intracellular neurofibrillary pathology. The increase in hexitol-lysine and CML can result from either lipid peroxidation or advanced glycation, whereas hexitol-lysine is solely a product of glycation, suggesting that two distinct oxidative processes act in concert in the neuropathology of the disease. Furthermore, using olfactory neurons as an experimental model, we observed an increase in glycation products in neurons derived from Alzheimer's disease patients. Our findings support the idea that aldehyde-mediated modifications, in concert with oxyradical-mediated modifications, are critical early pathogenic factors in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)545-552
Number of pages8
JournalAnnals of the New York Academy of Sciences
Volume1043
DOIs
StatePublished - 2005
Externally publishedYes

Keywords

  • Advanced glycation end products
  • Alzheimer's disease
  • Neurofibrillary tangles
  • Oxidative stress
  • Senile plaques

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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