Figure 3.

Illustration of the possible interactions between microglia, astrocytes, and neurons, during early and late stage ALS. The NF-κB pathway is activated in both astrocytes and microglia in ALS, but its effects differ between the stages of the disease. Pre-symptomatically, astrocytes with activated NF-κB promote neuroprotective M2-type microglial proliferation, while at a later stage a neurotoxic M1-type microglial phenotype is induced. Subsequently, M1 microglia cause axonal damage and promote motor neuron death. In addition, M1 microglia induce a neurotoxic astrocytic phenotype, leading astrocytes to decrease their synaptogenesis and promotion of neuronal survival.