Table 2.
Summary of protective and detrimental pathways of astroglial signaling.
| Mediated by | Function | Effect | References | |||
|---|---|---|---|---|---|---|
| Microglia activation | Inflammation | Neurodegeneration | ||||
| Protective microglia pathways | Glycoprotein gp130 Signal transducer for IL-6 cytokine family | Astrocyte’s survival | ↑ astrocytes-mediated apoptosis | = | ↓ | Haroon et al. (2011) |
| TGFβ signaling | Immuno-suppressive | ↓ proliferation | ↓ inhibition of NF-kB signaling | ↓ | Cekanaviciute et al. (2014) | |
| IFNyR through T and NK cells | Inflammatory regulation and immuno-suppressive | ↓ proliferation | ↓ down-regulation of iNOS, TNF, IL-10, and IL-27 | ↓ | Hindinger et al. (2012) | |
| NrF2 pathway | Anti-inflammatory and antioxidant | ↑ expression of antioxidant genes | ↓ suppression of cytokines | ↓ | Patel et al. (2017) | |
| BDNF through JAK-STAT3 pathway | Anti-inflammatory and neurotrophic | ↓ | ↓ suppression of cytokines | ↓ | O’Callaghan et al. (2014) | |
| Detrimental astrocyte pathways | BDNF through TRkB receptor and NF-kB pathway | Pro-inflammatory | ↑ increase of NO released by astrocytes | ↑ | ↑ | Colombo et al. (2012) |
| NFkB recruitment after IL-17 binding to its receptor | Release of pro-inflammatory cytokines and chemokines | ↑ | ↑ via astrocytic IL-17 pathway | ↑ | Brambilla et al. (2005) | |
| CCL2, CCL 21, CXCL10 via NF-kB signaling | Pro-inflammatory | ↑ | ↑ recruitment of infiltrating immune cells in CNS | ↑ | Brambilla et al. (2005, 2009), Kim et al. (2014), and Mills Ko et al. (2014) | |
| CXCL12 | Pro-inflammatory | ↑ | ↑ pro-inflammatory cytokines production | = | Bezzi et al. (2001) | |
| VEGF | Control of vascular permeability (BBB integrity) | = | ↑ recruitment of infiltrating immune cells in CNS | ↑ | Argaw et al. (2012) | |
The table reports the principal intracellular pathways involved in the regulation of astrocytes activity by dividing the protective and the detrimental role. It highlights the main function of astroglia, followed by the specific effect on cellular activation and the effect on the inflammatory and neurodegenerative condition. ↑ and ↓ represent upregulation and downregulation respectively, = means that the pathway does not affect that condition.