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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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
Volume47
Issue number6-7
DOIs
StatePublished - Jul 1 2013

Fingerprint

Intermediate Filaments
Lysine
Lipids
Labeling
Lipid Peroxidation
Axons
Neurofibrillary Tangles
Proteins
Oxidative stress
Amyloid Plaques
Sciatic Nerve
Immunoblotting
Aldehydes
Alzheimer Disease
Oxidative Stress
Solubility
Amino Acids
Antibodies
link protein

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Perry, E. A., Castellani, R. J., Moreira, P. I., Nunomura, A., Lui, Q., Harris, P. L. R., ... Perry, G. (2013). Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links. Free Radical Research, 47(6-7), 507-510. https://doi.org/10.3109/10715762.2013.794265

Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links. / Perry, E. A.; Castellani, R. J.; Moreira, P. I.; Nunomura, A.; Lui, Q.; Harris, P. L.R.; Sayre, L. M.; Szweda, P. A.; Szweda, L. I.; Zhu, X.; Smith, M. A.; Perry, George.

In: Free Radical Research, Vol. 47, No. 6-7, 01.07.2013, p. 507-510.

Research output: Contribution to journalArticle

Perry, EA, Castellani, RJ, Moreira, PI, Nunomura, A, Lui, Q, Harris, PLR, Sayre, LM, Szweda, PA, Szweda, LI, Zhu, X, Smith, MA & Perry, G 2013, 'Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links', Free Radical Research, vol. 47, no. 6-7, pp. 507-510. https://doi.org/10.3109/10715762.2013.794265
Perry EA, Castellani RJ, Moreira PI, Nunomura A, Lui Q, Harris PLR et al. Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links. Free Radical Research. 2013 Jul 1;47(6-7):507-510. https://doi.org/10.3109/10715762.2013.794265
Perry, E. A. ; Castellani, R. J. ; Moreira, P. I. ; Nunomura, A. ; Lui, Q. ; Harris, P. L.R. ; Sayre, L. M. ; Szweda, P. A. ; Szweda, L. I. ; Zhu, X. ; Smith, M. A. ; Perry, George. / Neurofilaments are the major neuronal target of hydroxynonenal-mediated protein cross-links. In: Free Radical Research. 2013 ; Vol. 47, No. 6-7. pp. 507-510.
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