Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle weakness and fatigue. Familial ALS is associated with inheritable mutations in the superoxide dismutase 1 enzyme, SOD1. Wang et al. now demonstrate that expression of mutant human SOD1 in the nematode C. elegans causes severe locomotor defects and paralysis in this model organism. They also show that the neuronal dysfunction is in part due to aberrant protein misfolding and aggregation of SOD1. This study demonstrates how this new C. elegans model of ALS can aid in understanding protein folding, neurodegeneration and the mechanisms underlying ALS pathology.
Wang J, Farr GW, Hall DH, Li F, Furtak K, Dreier L, Horwich AL (2009). An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of caenorhabditis elegans. PLoS Genet. 5, e1000350.
