FIGURE 9.

Hypothesis on the consequences of NGF signaling in glial cells. We propose that astrocytes are ambient NGF sensors. NGF levels (which include either mNGF, proNGF, or different ratios thereof) affect glial physiology. In particular, as reported in this work, decreasing concentration of NGF leads to an A1-activation of astrocytes and neurotoxicity (red neuron). On the contrary, as previously reported (Rizzi et al., 2018), increasing the concentrations of NGF steers microglia toward an anti-inflammatory phenotype, leading to neuroprotection (blue neuron). Of note, defining microglial cells as reactive or homeostatic is an oversimplification (Paolicelli et al., 2022) and we use such terms merely to indicate the neuroprotective effects of NGF via microglia.