Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease resulting in paralysis and usually death within less than 5 years of onset. Inherited forms of ALS are most often associated with expression of a dominant mutated form of superoxide dismutase (SOD1) which is toxic to motor neurons, causing them to die prematurely.
To determine the role of mutated SOD1 in the progression of ALS, Yamanaka et al. engineered a chimeric mouse model in which the expression of mutant SOD1 was isolated to motor neurons and oligodendrocytes. They report that the presence of the surrounding ‘normal’ cells, not expressing mutated SOD1, inhibits the progression of neurodegeneration and increases disease-free life span when compared with mice that ubiquitously express mutant SOD1.
This indicates that many different cell types, in addition to motor neurons and oligodendrocytes, contribute to the onset and progression of ALS and the interaction of cell types should be considered when determining the potential of future therapeutics.
