Fig. 3

Multiple system atrophy strain formation requires multiple insults. The formation of Multiple system atrophy-specific α-Synuclein strains is likely a multifactorial process requiring insults to both neurons and oligodendrocytes. Host characteristics and environmental factors may favor the upregulation and secretion of neuronal α-Syn, while the same factors may alter oligodendrocytes providing the necessary cellular environment for strain formation to occur. Additional oligodendrocyte-specific factors may be pivotal in determining the unique characteristics of Multiple system atrophy-specific strains. Once formed, these strains may induce glial cytoplasmic inclusions in oligodendrocytes or may be shuttled to neurons resulting in neuronal cytoplasmic inclusions