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We report increased modification of proteins by 4‐hydroxynoneal (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 preparatations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of gluatmate transport, and excitotoxic motor neuron degeneration in ALS.