E-4-HYDROXY-2-NONENAL IS CYTOTOXIC AND CROSS-LINKS CYTOSKELETAL PROTEINS IN P19 NEUROGLIAL CULTURES

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 m ostly of tau protein, contain cross-linked and ubiquitin-conjugated pr otein. 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 what were conjugated with ubiquitin. Ma londialdehyde formed monoadducts with cell protein but did not cross-l ink and was not cytotoxic. A non-cross-linking 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.