OXIDATIVE DAMAGE TO PROTEIN IN SPORADIC MOTOR-NEURON DISEASE SPINAL-CORD

The recent discovery that defects in the gene encoding copper-zinc sup eroxide dismutase (SOD1) are associated with some cases of familial mo tor neuron disease has heightened interest in the possibility that fre e radical mechanisms may contribute to selective motor neuron injury. Sporadic and familial motor neuron diseases are clinically and patholo gically very similar and may share common pathophysiological mechanism s, Thus the role of free radical mechanisms as a Contributory factor t o motor neuron injury in the common sporadic form of motor neuron dise ase requires urgent exploration, particularly as this may provide an a venue for therapy aimed at retarding pathological progression. We inve stigated oxidative damage to proteins in the lumbar spinal cord by qua ntifying the protein carbonyl level from 19 patients with sporadic mot or neuron disease, 8 neurologically normal control subjects, and 11 ne urological disease control subjects, most of whom had slowly progressi ve neurodegenerative disease. In sporadic motor neuron disease the mea n protein carbonyl level in the spinal cord was increased by 119% (P < 0.02) compared to normal control subjects and by 88% (P < 0.04) compa red to the neurological disease control subjects. These data contribut e to the emerging evidence that oxidative damage may play a contributo ry role in the neuronal death in sporadic motor neuron disease. This m echanism may be particularly important in a subset of patients with mo tor neuron disease.