Exosome: A novel neurotransmission modulator or non-canonical neurotransmitter?

Neurotransmission is the electrical impulse-triggered propagation of signals between neurons or between neurons and other cell types such as skeletal muscle cells. Recent studies point out the involvement of exosomes, a type of small bilipid layer-enclosed extracellular vesicles, in regulating neurotransmission. Through horizontally transferring proteins, lipids, and nucleic acids, exosomes can modulate synaptic activities rapidly by controlling neurotransmitter release or progressively by regulating neural plasticity including synapse formation, neurite growth & removal, and axon guidance & elongation. In this review, we summarize the similarities and differences between exosomes and synaptic vesicles in their biogenesis, contents, and release. We also highlight the recent progress made in demonstrating the biological roles of exosome in regulating neurotransmission, and propose a modified model of neurotransmission, in which exosomes act as novel neurotransmitters. Lastly, we provide a comprehensive discussion of the enlightenment of the current knowledge on neurotransmission to the future directions of exosome research.