Role of Mitochondrial Dysfunction in Motor Neuron Degeneration in ALS

Amyotrophic lateral sclerosis (ALS), which was described since 1869 by Jean Martin Charcot, is a devastating neurodegenerative disease characterized by the selective and progressive loss of upper and lower motor neurons of the cerebral cortex, brainstem and the spinal cord. Progressive motor neuron loss causes muscle weakness, spasticity and fasciculation, eventually paralysis and finally death by respiratory failure 3 to 5 years after diagnosis. ALS worldwide prevalence is about 2 to 8 people per 100,000, and presents two important differences with respect to other neurogenerative diseases: the cognitive process is not affected and is not merely the result of aging because may occur at young ages (Chancellor & Warlow, 1992; Huisman et al., 2011). Two forms of ALS are known, the familial type (FALS), associated with genetic mutations, mainly in the gene encoding superoxide dismutase 1 (SOD1, enzyme responsible for superoxide dismutation to oxygen and hydrogen peroxide), and the sporadic form (SALS), of unknown origin. FALS represents only about 5-10% of cases (Rosen et al., 1993; Rowland & Shneider, 2001), and SALS comprises the remaining 90%. Despite having different origins, both ALS types develop similar histopathological and clinical characteristics.