In Vivo and In Vitro Models to Study Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset neurodegenerative disorder characterized by the death of large motor neurons in the cerebral cortex and spinal cord (Tandan and Bradley, 1985). Dysfunction and death of these cell populations lead to progressive muscle weakness, atrophy, fasciculations, spasticity and ultimately, paralysis and death usually within 3 to 5 years after disease onset (Mulder, 1982). The estimated worldwide incidence for this disease is around 2 per 100,000 in the general population and the life-long risk to develop ALS is approximately 1:2000. The disease occurs in sporadic (90%) and familial forms (10%) (Gros-Louis, et al., 2006). With the exception of few FALS cases in which other neurodegenerative disorders can simultaneously occur, FALS and SALS are clinically indistinguishable. To date, mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have remained the major known genetic causes associated with ALS. However, the mechanism whereby mutant SOD1 causes specific degeneration of motor neurons remains unclear. Nonetheless, many neuronal death pathways have been revealed through studies with transgenic mice expressing SOD1 mutants. Other vertebrate, invertebrate and in vitro models of ALS have also been described. Here, we will review various animal and cellular models that have been used to study the toxicity of ALS-linked gene mutations and also to investigate pathological hallmarks of the disease.