ABSTRACT
Although neurons, particularly motor neurons, are susceptible to the pathophysiologic process in amyotrophic lateral selerosis (ALS) and eventually undergo degeneration, there is increasing experimental evidence to suggest an important role for nonneuronal cell populations in contributing to neuronal dysfunction and the disease phenotype. Within the central nervous system (CNS), neurons exist in close contact with a variety of other cell types including astrocytes, oligodendrocytes, and microglia, while motor neuron axons projecting into the periphery are in proximity with Schwann cells and, of course, muscle. These differing nonneuronal cell types can be affected directly by the disease process in ALS, thereby contributing directly to the overall phenotype, or nonneuronal cells might indirectly impact neuron survival and function. Evidence for non-neuronal cell involvement in ALS has arisen directly from studies using autopsied human tissue from patients with sporadic and familial forms of ALS. However, more definitive insights have come from experiments using mutant Cu,Zn superoxide dismutase (SOD1) transgenic mice that serve as an excellent model of one inherited form of ALS. This animal model has allowed novel genetic approaches to be used in evaluating the role of nonneuronal cells to the ALS disease process, which has potential treatment implications for human ALS.
