Extracellular Vesicle-Mediated Cell⁻Cell Communication in the Nervous System: Focus on Neurological Diseases

Abstract

Extracellular vesicles (EVs), including exosomes, are membranous particles released by cells into the extracellular space. They are involved in cell differentiation, tissue homeostasis, and organ remodelling in virtually all tissues, including the central nervous system (CNS). They are secreted by a range of cell types and via blood reaching other cells whose functioning they can modify because they transport and deliver active molecules, such as proteins of various types and functions, lipids, DNA, and miRNAs. Since they are relatively easy to isolate, exosomes can be characterized, and their composition elucidated and manipulated by bioengineering techniques. Consequently, exosomes appear as promising theranostics elements, applicable to accurately diagnosing pathological conditions, and assessing prognosis and response to treatment in a variety of disorders. Likewise, the characteristics and manageability of exosomes make them potential candidates for delivering selected molecules, e.g., therapeutic drugs, to specific target tissues. All these possible applications are pertinent to research in neurophysiology, as well as to the study of neurological disorders, including CNS tumors, and autoimmune and neurodegenerative diseases. In this brief review, we discuss what is known about the role and potential future applications of exosomes in the nervous system and its diseases, focusing on cell⁻cell communication in physiology and pathology.

Keywords: biomarkers; cell–cell interaction; central nervous system; exosomes; extracellular vesicles; nervous system; neurological diseases; theranostics tools.

Figure 1

Cells of the central and peripheral nervous systems. These cells have functions and locales of residence distinctive of each of them but they all can secrete exosomes and receive exosomes from the others, as depicted in Figure 2. BBB: blood–brain barrier.

Figure 2

Schematic representation of the nervous tissue and exosome traffic. Some of the cells presented in Figure 1 are here seen in the central nervous tissue along with a blood vessel. Also present are epithelial cells lining the inside of the blood vessel, the blood–brain barrier (BBB) separating the lumen of the vessel from the nervous tissue, and exosomes secreted by the four types of nervous cells shown. Exosomes follow different routes, as indicated by double parallel arrows, from one cell to another or through the BBB they gain the general circulation and reach distant targets. Conversely, exosomes can traverse the BBB from inside the vessel into the nervous tissue and reach any of the nervous cell types in it.

Figure 3

Diagrammatic representation of the various groups encompassing the neurological diseases presented in Table 1. It can be seen that according to their main etiopathogenic feature, neurological diseases can be classified into distinct groups. However, there are various examples in which a disease can be classified into more than one group because the etiopathogenic features are mixed, or incompletely understood. Abbreviations: AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; DIPG, diffuse intrinsic pontine gliomas; EP, ependymoma; GB, glioblastoma; MB, medulloblastoma; MPNSTs, malignant peripheral nerve sheath tumors; MS, multiple sclerosis; PD, Parkinson’s disease.