Neurotoxicity Research

, Volume 22, Issue 4, pp 251–264

Nitric Oxide-Mediated Oxidative Damage and the Progressive Demise of Motor Neurons in ALS

  • Derek A. Drechsel
  • Alvaro G. Estévez
  • Luis Barbeito
  • Joseph S. Beckman
Review Article

DOI: 10.1007/s12640-012-9322-y

Cite this article as:
Drechsel, D.A., Estévez, A.G., Barbeito, L. et al. Neurotox Res (2012) 22: 251. doi:10.1007/s12640-012-9322-y


Oxidative damage is a common and early feature of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders. Dr. Mark Smith and his colleagues have built the case for oxidative stress being a primary progenitor rather than a secondary end-stage epiphenomenon of neurodegeneration. They proposed that reactive oxygen species contribute to the “age-related cascade of neurodegeneration,” whereby accumulative oxidative damage with age promotes other characteristic pathological changes in afflicted brain regions, including protein aggregation, metabolic deficiencies, and inflammation. Nitric oxide (NO) likely plays a critical role in this age-related cascade. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through stimulating cyclic GMP synthesis. However, the same physiological concentrations of NO, relevant in cellular signaling, may also initiate and amplify oxidative damage by diffusion-limited reactions with superoxide (O2•−) to produce peroxynitrite (ONOO). This is perhaps best illustrated in ALS where physiological levels of NO promote survival of motor neurons, but the same concentrations can stimulate motor neuron apoptosis and glial cell activation under pathological conditions. While these changes represent a complex mechanism involving multiple cell types in the pathogenesis of ALS, they also reveal general processes underlying neurodegeneration.


Nitric oxidePeroxynitriteAmyotrophic lateral sclerosisNeurodegenerationProtein nitration

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Derek A. Drechsel
    • 1
    • 2
  • Alvaro G. Estévez
    • 3
  • Luis Barbeito
    • 4
    • 5
  • Joseph S. Beckman
    • 2
    • 6
  1. 1.Department of Environmental and Molecular ToxicologyOregon State UniversityCorvallisUSA
  2. 2.Environmental Health Sciences CenterOregon State UniversityCorvallisUSA
  3. 3.Burnett School of Biomedical SciencesUniversity of Central FloridaOrlandoUSA
  4. 4.Instituto de Investigaciones Biologicas EstableMontevideoUruguay
  5. 5.Institut Pasteur de MontevideoMontevideoUruguay
  6. 6.Linus Pauling InstituteOregon State UniversityCorvallisUSA