Role of endogenous nitric oxide and peroxynitrite formation in the survival and death of motor neurons in culture

Prog Brain Res. 1998;118:269-80. doi: 10.1016/s0079-6123(08)63214-8.

Abstract

Motor neuron survival is highly dependent on trophic factor supply. Deprivation of trophic factors results in induction of neuronal NOS, which is also found in pathological conditions. Growing evidence suggests that motor neuron degeneration involves peroxynitrite formation. Trophic factors modulate peroxynitrite toxicity (Estévez et al., 1995; Shin et al., 1996; Spear et al., 1997). Whether a trophic factor prevents or potentiates peroxynitrite toxicity depends upon when the cells are exposed to the trophic factor (Table 1). These results strongly suggest that a trophic factor that can protect neurons under optimal conditions, but under stressful conditions can increase cell death. In this context, it is possible that trophic factors or cytokines produced as a response to damage may potentiate rather than prevent motor neuron death. A similar argument may apply to the therapeutic administration of trophic factors to treat neurodegenerative diseases. Similarly, the contrasting actions of NO on motor neurons may have important consequences for the potential use of nitric oxide synthase inhibitors in the treatment of ALS and other related neurodegenerative diseases.

Publication types

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

MeSH terms

  • Amyotrophic Lateral Sclerosis / enzymology
  • Amyotrophic Lateral Sclerosis / genetics
  • Animals
  • Apoptosis
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Death
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Humans
  • Motor Neurons / cytology
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Nitrates / metabolism
  • Nitrates / physiology*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Superoxide Dismutase / genetics
  • Tyrosine / analogs & derivatives
  • Tyrosine / physiology

Substances

  • Brain-Derived Neurotrophic Factor
  • Nitrates
  • peroxynitric acid
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Superoxide Dismutase