Figure 9.

Proposed model for the cellular effects of α-SYN accumulation in astrocytes. Ingested α-SYN oligomers are transported to early/late endsosomes (A), but the lysosomal degradation is not completed (B). Instead, the aggregated α-SYN is stored intracellularly in the TGN region (C). The α-SYN accumulation is clearly stressful for the cell and results in swollen ER (D) and mitochondria fragmentation (E). Impaired mitochondria are initially degraded by the autophagosomes (F). However, the mitophagy is insufficient and pathological mitochondria remain in the astrocyte. Moreover, α-SYN oligomer-exposed astrocytes rapidly deploy a “defense mechanism” that consists of sending out TNTs to other astrocytes, enabling direct intercellular transmission of the toxic protein to healthy astrocytes (G). In return, healthy astrocytes send mitochondria to “rescue” stressed astrocytes (H).