Progressive Motor Neuron Impairment in an Animal Model of Familial Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration and loss of motor neurons in the anterior horn and the brainstem and, to a variable extent, degeneration of the descending motor pathways within the corticospinal tracts (1,2). This disorder leads to progressive muscular atrophy, weakness, paralysis and eventually death due to respiratory failure (3). ALS occurs in both familial (FALS) and sporadic forms (SALS). FALS accounts for only 5–10% of the cases, with an autosomal dominant pattern of inheritance (4, 5). Approximately 20% of the FALS have been associated with mutations in SOD1, the gene that encodes for cytosolic Cu,Zn Superoxide dismutase (SOD)(6, 7, 5). Two mechanisms by which SOD1 mutants cause the disease have been proposed: loss of enzyme function or gain of a new function. In SALS, on the other hand, a deficiency in glutamate transport in brain has been suggested (8, 9).