Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links

E. A. Perry, R. J. Castellani, P. I. Moreira, A. Nunomura, Q. Lui, P. L.R. Harris, L. M. Sayre, P. A. Szweda, L. I. Szweda, X. Zhu, M. A. Smith, George Perry*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Lipid peroxidation generates reactive aldehydes, most notably hydroxynonenal (HNE), which covalently binds amino acid residue side chains leading to protein inactivation and insolubility. Specific adducts of lipid peroxidation have been demonstrated to be intimately associated with pathological lesions of Alzheimer's disease (AD), suggesting that oxidative stress is a major component in the disease. Here, we examined the HNE-cross-linking modifications by using an antibody specific for a lysine-lysine cross-link. Since in a prior study we noted no immunolabeling of neuritic plaques or neurofibrillary tangles but instead found strong labeling of axons, we focused this study on axons. Axonal labeling was examined in mouse sciatic nerve, and immunoblotting showed the cross-link was restricted to neurofilament heavy and medium subunits, which while altering migration, did not indicate larger NF aggregates, indicative of intermolecular cross-links. Examination of mice at various ages showed the extent of modification remaining relatively constant through the life span. These findings demonstrate lipid-cross-linking peroxidation primarily involves lysine-rich neurofilaments and is restricted to intramolecular cross-links.

Original languageEnglish (US)
Pages (from-to)507-510
Number of pages4
JournalFree Radical Research
Issue number6-7
StatePublished - Jul 2013


  • Alzheimer disease
  • Axon
  • Cytoskeleton
  • Lipid peroxidation
  • Neurofibrillary tangle
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry


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