Fig. 3

Receptor-mediated phagocytosis of amyloidogenic proteins and processing in astrocytes. The figure recapitulates the different receptors able to interact with α-Syn and Tau, as described in the text. Once recognized by the appropriate receptor(s), α-Syn and Tau are enclosed into phagosomes, which fuse with lysosomes into phago-lysosomes, and subsequently degraded. However, likely due to a high pH into the phagolysosomes, astrocytes cannot perform a complete digestion of the phagocytosed material, which can then be accumulated and released in the extracellular space as free molecules (1) or within vesicles (2). Moreover, the progressive accumulation of α-Syn and Tau can lead to mitochondrial damage (3) or to the formation of deposits (4) that, together with the activation of TLRs (5) can induce a pro-inflammatory phenotype of the astrocytes. Furthermore, astrocytes can expose partially digested antigens on MHC-I, MHC-II or CD40 molecules (6), thus working as antigen presenting cells