FIGURE 9.

Plasma exosomes impair microglial degradation of α‐synuclein through V‐ATPase subunit V1G1. Plasma‐derived exosomes from patients with PD contain toxic α‐syn and PD‐exo downregulates lysosomal V1G1 expression; PD‐exo alternated the amount, morphology, and distribution of lysosomes in microglia and impaired the activity of hydrolytic enzymes in the lumen; PD‐exo augmented the accumulation of pathological α‐syn within microglia and induced NLRP3‐mediated neuroinflammation; and V1G1 deficiency impaired lysosomal function, leading to further aggregation of α‐syn in microglia and inflammation.