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

Ward A. Pedersen, Weiming Fu, Jeffrey N. Keller, William R. Markesbery, Stanley Appel, R. Glenn Smith, Edward Kasarskis, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid perodixation, 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 or 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.

Original languageEnglish (US)
Pages (from-to)819-824
Number of pages6
JournalAnnals of Neurology
Volume44
Issue number5
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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