PROTEIN MODIFICATION BY THE LIPID-PEROXIDATION PRODUCT 4-HYDROXYNONENAL IN THE SPINAL-CORDS OF AMYOTROPHIC-LATERAL-SCLEROSIS PATIENTS

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 o f neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral horn motor neurons, and immunopr ecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the functi on of proteins modified by HNE can be severely compromised as previous ly demonstrated for glutamate transporters in cortical synaptosome pre parations, our findings suggest a scenario in which oxidative stress l eads to the production of HNE, impairment of glutamate transport, and excitotoxic motor neuron degeneration in ALS.