Chapter 19 Role of endogenous nitric oxide and peroxynitrite formation in the survival and death of motor neurons in culture

This chapter describes the role of endogenous nitric oxide and peroxynitrite formation in the survival and death of motor neurons in culture. The selective degeneration of motor neurons is the predominant pathological finding in amyotrophic lateral sclerosis (ALS) and a variety of spinal atrophies. Motor neuron survival is dependent on trophic factor supply. Deprivation of trophic factors results in the induction of neuronal NOS, which is also found in pathological conditions. Motor neuron degeneration involves peroxynitrite formation. Trophic factors modulate peroxynitrite toxicity. Whether a trophic factor prevents or potentiates peroxynitrite toxicity depends upon when the cells are exposed to the trophic factor. The results suggest that a trophic factor that can protect neurons under optimal conditions can increase cell death under stressful conditions. Trophic factors or cytokines produced as a response to damage may potentiate rather than prevent motor neuron death.