**1. Introduction**

312 Amyotrophic Lateral Sclerosis

Yim, M.B.; Kang, J.H.; Yim, H.S.; Kwak, H.S.; Chock, P.B. & Stadtman, E.R. (1996). A gain-of-

*United States of America,* Vol.93, No.12, pp. 5709–5714

function of an amyotrophic lateral sclerosis-associated Cu,Zn-superoxide dismutase mutant: an enhancement of free radical formation due to a decrease in Km for hydrogen peroxide. *Proceedings of the National Academy of Sciences of the* 

> Nitric oxide is a cellular messenger produced by different cell types in an organism, both in physiological and pathological conditions (Snyder 1993; Beckman and Koppenol 1996; Beckman and Koppenol 1996; Beckman 1996; Colasanti and Suzuki 2000; Pacher, Beckman, and Liaudet 2007). Nitric oxide was first described in biology as the endothelium-derived relaxation factor for its effects on vasodilatation (Ignarro 1990), but soon become evident it have other important physiological functions such as a retrograde messenger in the nervous systems, and during the immune response (Moncada, Palmer, and Higgins 1991). Nitric oxide can also regulate mitochondria respiration (Carreras and Poderoso 2007; Ramachandran et al. 2002), and reacts with oxygen and reactive oxygen species to form reactive nitrogen species, which in turn can damage the cells. The reactivity of nitric oxide and the metabolic state of the cell or tissue are determining factors on the specific actions mediated by nitric oxide. It is not our intention to examine the biochemistry and physiology of nitric oxide, which has been cover in several excellent reviews (Beckman and Crow 1993; Beckman 1996; Pacher, Beckman, and Liaudet 2007), but to concentrate in those nitric oxidederivate species relevant to the regulation of motor neuron apoptosis. However, some relevant aspects of the biochemistry of nitric oxide will be reviewed as the necessary background to understand the biology of reactive nitrogen species in motor neurons.
