Fig. 9

Hypothesis of the effects of treatment with LV-NR-R80Q-apoB in MBP-α-syn tg mice. In the MBP-α-syn tg model of MSA, oligodendrocytes express high levels of α-syn and release it to the extracellular environment, where it can propagate to astroglial cells or be taken up by microglial cells for degradation. The modified, brain-targeted fusion protein NR-R80Q-apoB (neurosin-apoB) is able to access and degrade extracellular α-syn, as well as be internalized by astroglia and microglia, potentially degrading also intracellular α-syn in those cell types. In LV-Control-treated tg mice (a), α-syn propagates and accumulates within astroglial cells. However in LV-NR-R80Q-apoB-treated tg animals neurosin degrades extracellular α-syn (b), thus stimulating further release of α-syn from oligodendroglial cells (“sink effect”), reducing its propagation and accumulation in astroglia, and inducing its uptake and degradation by microglia