FIG. 5.

Physiology, pathology, and paracrine effects of EVs in the central nervous system. (I) Astrocyte-secreted EVs stimulate dendritic arborization of neurons through synapsin; (II) EVs from microglia increase neuronal synaptic activity; (III) EVs from neurons activate glial cell function, such as phagocytosis of inactive synapses and toxic proteins (e.g., Aβ); (IV) EVs from oligodendrocytes enhance stress tolerance of neurons and stimulate anterograde transport of signaling molecules for myelination such as PLP; (V) EVs also participate in early brain development through proteins released from immature neural progenitor cells, such as L1 adhesion molecule, GPI-anchored prion protein, and the GluR2/3 subunit of glutamate receptor; (VI) Retrotransposon transportation between cells occur through EV compartment. In neurodegenerative diseases, EVs promote (VII) cell-to-cell spreading and (VIII) accumulation of toxic proteins such as tau, SOD1, TDP-43, and prions. Aβ, amyloid beta; GPI, glycosylphosphatidylinositol; PLP, proteolipoprotein. Revised from Zappulli et al.⁹⁹ Color images are available online.