Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding - PubMed
3 days ago
- #Amyotrophic lateral sclerosis
- #superoxide dismutase-1
- #prion
- Mutations in SOD1 cause familial amyotrophic lateral sclerosis (ALS) by promoting misfolding into neurotoxic aggregates.
- Previous studies showed that G85R SOD1 mice develop paralysis faster after injection of spinal homogenates from paralyzed G85R SOD1 mice, indicating prion-like propagation.
- G93A SOD1 mice, which typically develop paralysis by 6 months, were initially resistant to seeding by homogenates from paralyzed G93A mice.
- A low-expressing G93A SOD1 mouse line (VLE-G93A) showed responsiveness to seeding but at low efficiency.
- The study found that adult VLE G93A SOD1 mice (up to 12 months old) injected intrathecally with seeding homogenates containing misfolded G93A or G85R SOD1 developed accelerated motor neuron disease efficiently.
- The efficiency of SOD1 seeding to induce motor neuron disease in VLE G93A SOD1 mice is influenced by the route and age of inoculation.
- The findings suggest that prion-like templating contributes to disease progression in SOD1-ALS.