Role of exosomes/microvesicles in the nervous system and use in emerging therapies

Abstract

Extracellular membrane vesicles (EMVs) are nanometer sized vesicles, including exosomes and microvesicles capable of transferring DNAs, mRNAs, microRNAs, non-coding RNAs, proteins, and lipids among cells without direct cell-to-cell contact, thereby representing a novel form of intercellular communication. Many cells in the nervous system have been shown to release EMVs, implicating their active roles in development, function, and pathologies of this system. While substantial progress has been made in understanding the biogenesis, biophysical properties, and involvement of EMVs in diseases, relatively less information is known about their biological function in the normal nervous system. In addition, since EMVs are endogenous vehicles with low immunogenicity, they have also been actively investigated for the delivery of therapeutic genes/molecules in treatment of cancer and neurological diseases. The present review summarizes current knowledge about EMV functions in the nervous system under both physiological and pathological conditions, as well as emerging EMV-based therapies that could be applied to the nervous system in the foreseeable future.

Keywords: cancer; development; exosomes; microvesicles; neurodegeneration; neuron; neuroregeneration; therapy.

Figure 1

Extracellular membrane vesicles-mediated mechanisms in neurons. (A) A gradient of EMVs in the developing nervous system can serve as a directional guide to axonal growth. (B) EMVs released from presynaptic nerve terminals and taken up by their postsynaptic partners can carry informational content which can modulate the strength of synaptic activity. (C) Regeneration of peripheral nerves in enhanced by the EMV transfer of ribosomes and mRNA directly from surrounding Schwann cells into the injured nerve to promote protein synthesis.

Figure 2

Extracellular membrane vesicles-based therapies. (A) EMV immunotherapy. EMVs containing tumor-antigen within and/or on the membrane surface are isolated from different sources and introduced in vivo to elicit targeted immune responses. (B) EMV RNAi therapy. EMVs derived from immature dendritic cells (DCs) expressing Rabies glycoprotein-Lamp2b fusion protein were electroporated with siRNAs for targeting against neurons, microglia, and oligodendrocytes for subsequent gene silencing (Alvarez-Erviti et al., 2011). (C) EMV drug therapy. Therapeutic compounds can be packaged into/onto EMVs isolated from donor cells to minimize degradation and increase delivery to intended sites.