Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients

Ann Neurol. 1998 Nov;44(5):819-24. doi: 10.1002/ana.410440518.


We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral horn motor neurons, and immunoprecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the function of proteins modified by HNE can be severely compromised as previously demonstrated for glutamate transporters in cortical synaptosome preparations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of glutamate transport, and excitotoxic motor neuron degeneration in ALS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aldehydes / analysis
  • Aldehydes / metabolism*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / pathology
  • Antibodies, Monoclonal
  • Autopsy
  • Cross-Linking Reagents
  • Humans
  • Immunohistochemistry
  • Lipid Peroxidation*
  • Middle Aged
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism*
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology


  • Aldehydes
  • Antibodies, Monoclonal
  • Cross-Linking Reagents
  • Nerve Tissue Proteins
  • 4-hydroxy-2-nonenal