Defective neurite outgrowth in aphidicolin/cAMP-induced motor
neurons expressing mutant Cu/Zn superoxide dismutase.
Lee KW, Kim HJ, Sung JJ, Park KS, Kim M.
Department of Neurology, Neuroscience Center, Seoul National University and
Biomedical Research Center, Korean National Institute of Health, Seoul, South
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
characterized by motor neuron involvement. Mutations in the human Cu/Zn
superoxide dismutase (SOD1) gene are found in some cases of familial ALS. Many
studies have reported SOD1 mutation-related neurodegeneration. However, whether
or not a mutant SOD1 affects neural development has not been demonstrated. We
developed motor neuron-neuroblastoma hybrid cells that expressed a mutant (G93A)
or the wild type (WT) SOD1. Cells were differentiated by dibutyryl cAMP and
aphidicolin. The mutant showed a defect in neurite outgrowth and had decreased
viability. Cytochrome c released and nuclear fragmentation were observed.
Western blot analysis showed that the amount of neurofilament and microtubule
associated proteins-2 (MAP-2) decreased during differentiation. These results
suggest that the defect in neurite outgrowth of mutant SOD1 cells is a
cytoskeletal defect and is associated with neuronal death.