FIGURE 1.

Both microglia and astrocytes have been shown to interact with alpha-synuclein. Among the different receptors suggested to play a role in such interaction, a special focus has been put on TLR4 and TLR2. In microglia, TLR4 seems to be involved in alpha-synuclein clearance, whereas TLR2 rather participates in the production of pro-inflammatory mediators. In astroglia, both receptors have been reported to play a role in the pro-inflammatory response to alpha-synuclein, with no proof of an involvement of TLR4 in the uptake of the protein by this cell type. Both microglia and astroglia can internalize alpha-synuclein. It seems however that, despite their capability to also degrade it in normal conditions, this process might get impaired in alpha-synucleinopathies, probably due to the overload of pathogenic alpha-synuclein, with consequent accumulation of the protein in glial cells. This might lead to their dysfunction and an enhanced neurotoxic profile. Other receptors, and related pathways, have also been associated with glial responses to alpha-synuclein. Further studies are warranted to highlight alternative mechanisms involved in these processes. The interplay between glial cells seems to be relevant as well. Astrocytes, through the release of specific sets of chemokines and cytokines, are able to attract microglia and influence their activation state. On the other hand, recent evidence indicates that also microglia can induce specific astroglial profiles, which can actively affect the pathology progression.