Fast and slow strains of misfolded superoxide dismutase 1 in amyotrophic lateral sclerosis

Most SOD1 ALS cases show a 2-5 year clinical course, but a subset of patients exhibit a slowly progressing illness lasting 10-20 years. Substantial evidence indicates that disease-causing mutations in SOD1 promote misfolding and aggregation.

Spinal tissue homogenates from paralyzed transgenic mice containing misfolded mutant SOD1 accelerate paralysis when injected into the spine or sciatic nerve of young mutant SOD1 transgenic mice. Using this prion-like seeding model in G85R-SOD1:YFP transgenic mice to initiate the disease process, we show that human SOD1 variants associated with rapidly progressing ALS produce SOD1-ALS strains that cause paralysis earlier than mutations associated with slowly progressing disease.