Fig. 2

Proposed mechanism of nerve-injury-induced activation of neuregulin-1 leads to spread of disease. In the presence of mutant SOD1 protein, nerve injury produces a heightened, NRG-induced inflammatory response leading to a permanent loss of synapses that spreads up and down the spinal cord and resulting in progressive neurodegeneration. Results summarized in Fig. 1 suggest that this inflammatory response starts with microglia followed by a second wave of astroglial reactivity that correlates with a significant loss of motor neuron synaptic inputs