Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis

Ann Neurol. 1997 Oct;42(4):644-54. doi: 10.1002/ana.410420416.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Antibodies, Monoclonal
  • Family Health
  • Female
  • Humans
  • Male
  • Middle Aged
  • Motor Neurons / chemistry
  • Motor Neurons / enzymology
  • Mutation
  • Nissl Bodies
  • Nitrophenols / analysis
  • Oxidative Stress
  • Phenylacetates / analysis
  • Spinal Cord / chemistry
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • Superoxide Dismutase / genetics
  • Tyrosine / analogs & derivatives*
  • Tyrosine / analysis
  • Tyrosine / immunology
  • Tyrosine / metabolism


  • Antibodies, Monoclonal
  • Nitrophenols
  • Phenylacetates
  • 4-hydroxy-5-nitrophenyl acetic acid
  • 3-nitrotyrosine
  • Tyrosine
  • Superoxide Dismutase