E-4-hydroxy-2-nonenal is cytotoxic and cross-links cytoskeletal proteins in P19 neuroglial cultures.

Journal Article (Journal Article)

Lipid peroxidation increases with age in brain and is elevated further in Alzheimer's disease. E-4-hydroxy-2-nonenal and malondialdehyde are products of lipid peroxidation that can adduct and cross-link protein. Neurofibrillary tangles, a feature of Alzheimer's disease composed mostly of tau protein, contain cross-linked and ubiquitin-conjugated protein. In P19 neuroglial cultures, E-4-hydroxy-2-nonenal was a potent cytotoxin that cross-linked cytoskeletal proteins, including tau into high molecular weight species that were conjugated with ubiquitin. Malondialdehyde formed monoadducts with cell protein but did not cross-link and was not cytotoxic. A non-crosslinking analogue of E-4-hydroxy-2-nonenal was not cytotoxic. E-4-Hydroxy-2-nonenal may contribute to neurodegeneration and neurofibrillary tangle formation in Alzheimer's disease.

Full Text

Duke Authors

Cited Authors

  • Montine, TJ; Amarnath, V; Martin, ME; Strittmatter, WJ; Graham, DG

Published Date

  • January 1996

Published In

Volume / Issue

  • 148 / 1

Start / End Page

  • 89 - 93

PubMed ID

  • 8546230

Pubmed Central ID

  • PMC1861611

International Standard Serial Number (ISSN)

  • 0002-9440


  • eng

Conference Location

  • United States