nitrophenols and Amyotrophic-Lateral-Sclerosis

The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Antibodies, Monoclonal; Family Health; Female; Humans; Male; Middle Aged; Motor Neurons; Mutation; Nissl Bodies; Nitrophenols; Oxidative Stress; Phenylacetates; Spinal Cord; Superoxide Dismutase; Tyrosine