Figure 2.

MSA pathology may spread between anatomically connected regions as a result of reciprocal rounds of α-syn release and neuroinflammation. Neuronal dysfunction can lead to α-syn aggregation and release of α-syn aggregates, which can then interact directly with astrocytes and microglia to mediate activation. In turn, the release of pro-inflammatory factors by activated glia can act back on neurons to cause stress, thereby stimulating the formation and release of additional α-syn aggregates.