Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment

Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes progressive paralysis. While genetics play a role, environmental factors, such as injuries, may trigger or worsen the condition. The disease often starts in one area of the body and spreads, but the mechanisms behind this spread are unclear. Animal models suggest that nerve injuries can initiate the disease process. The glial growth factor neuregulin-1 may contribute to the spread of neuroinflammation, leading to neurodegeneration up and down the spinal cord. Drugs that block neuregulin-1 signaling could potentially slow down or stop the spread of the disease. This approach may offer a new therapeutic avenue for ALS, regardless of the underlying genetic cause.

• 1
  Nerve injury can hasten functional decline and shorten survival in SOD1 rat models of ALS, suggesting injury can initiate earlier disease onset and promote local spread.
• 2
  Increased and prolonged microglial inflammatory response followed by earlier and more pronounced astrocytic recruitment was observed in SOD1 animals versus controls after nerve injury.
• 3
  Aberrant NRG1 signaling has been shown in human tissues and animal models of ALS, with phosphorylated NRG1 receptors observed on activated microglia in the spinal cords.