Amyotrophic lateral sclerosis pathogenesis

Malaspina A, de Belleroche J (2004) Spinal cord molecular profiling provides a better understanding of amyotrophic lateral sclerosis pathogenesis. Brain Res Brain Res Rev 45 213-229. 

The excessive activity of excitatory amino acids, such as L-glutamate and L-aspartate, followed by elevation of intracellular free Ca2+ concentration and accumulation of free radicals has been postulated to underlie the neurodegeneration that occurs after ischemic insults and trauma. Additionally, an excitotoxic component has been shown to play an important role in the pathogenesis of chronic neurodegenerative disorders, such as Alzheimer s disease, Parkinson s disease, amyotrophic lateral sclerosis, and Huntington s disease, which are characterized by progressive loss of neuronal elements. 

A key feature of CuZnSOD is the maintenance of high dismutase activity while shielding the active site copper from other redox transformations [55]. However, it has been repeatedly suggested that apart from its main activity, CuZnSOD shows other enzymatic activities. One reason for these suggestions involved the role of CuZnSOD mutations in the pathogenesis of amyotrophic lateral sclerosis (see Sect. 1.9). 

Casoni, R, M. Basso, T. Massignan et al. Protein nitration in a mouse model of familial amyotrophic lateral sclerosis Possible multifunctional role in the pathogenesis. 

J. D. Rothstein. Excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis. Adv.Neurol. 68 7-20,1995. 

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