Extracellular Vesicles and a Novel Form of Communication in the Brain

Abstract

In numerous neurodegenerative diseases, the interplay between neurons and glia modulates the outcome and progression of pathology. One particularly intriguing mode of interaction between neurons, astrocytes, microglia, and oligodendrocytes is characterized by the release of extracellular vesicles that transport proteins, lipids, and nucleotides from one cell to another. Notably, several proteins that cause disease, including the prion protein and mutant SOD1, have been detected in glia-derived extracellular vesicles and observed to fuse with neurons and trigger pathology in vitro. Here we review the structural and functional characterization of such extracellular vesicles in neuron-glia interactions. Furthermore, we discuss possible mechanisms of extracellular vesicle biogenesis and release from activated glia and microglia, and their effects on neurons. Given that exosomes, the smallest type of extracellular vesicles, have been reported to recognize specific cellular populations and act as carriers of very specialized cargo, a thorough analysis of these vesicles may aid in their engineering in vitro and targeted delivery in vivo, opening opportunities for therapeutics.

Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells

“…This discrepancy could be due to a different tumor origin and to the type of EVs analysed, MVs in the quoted paper and the exosomes in our work. MVs bud directly from the plasma membrane, which blebs and packages the cellular components in defined structures that are then released into the extracellular environment upon cell activation, whereas exosomes derive from the inward budding of the late endosome, or multivesicular bodies, and are a more homogeneous population [17]. Therefore, although the overall function of tumor-derived EVs seems to support tumor escape, our results suggest that the biological effect on fractionated immune cells could vary accordingly to the type of vesicles analysed [36].…”

“…Exosomes are present in the blood and in other bodily fluids together with other extracellular vesicles (EVs) of different size, intracellular origin and composition, such as micro vesicles (MVs) (100–1000 nm) and apoptotic bodies that are released during cell death (500–2000 nm) [15]. EVs have been found to be released by GBM cells in which they represent a key mechanism of intracellular signalling able to support GBM cell proliferation, invasiveness, and chemo resistance as well as neoangiogenesis stimulation [16,17]. An increasing number of studies indicate that the physio-pathological role of tumor-derived EVs, including exosomes, might be in favour of supporting immune-suppression, as they contribute to the cancer progression by acting on a variety of immune cell types, including effector T cells, naturally occurring T-reg cells and NK cells [18,19].…”

Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on HIV-associated neurological complications

“…114 Accumulating evidence further suggests a key role of EVs in both the pathogenesis and propagation of prion diseases. 115, 116, 117 One of the initial studies has demonstrated that PRNP-expressing cell line (RK13) robustly secreted PRNP through exosomes. 118 Vella et al 119 further showed that exosomes released from PRNP-infected neuronal cell line (GT1-7) also induced prion propagation in both neuronal as well as non-neuronal cells.…”

Exosomes in Viral Disease

“…In appearance, exosomes are unilamellar vesicles composed of a lipid bilayer that have a homogenous cup-shaped appearance on scanning electromicroscopy [3,12]. To date, they can be shown to originate from almost every cell type studied, including, but not limited to, T cells [13], B cells [14,15], dendritic cells [16], neurons [17], astrocytes [18,19], endothelial cells [20], smooth muscle cells [21], oligodendrocytes [22], and reticulocytes [2,23]. The wide variety of cells that can excrete exosomes also dictates the wide array of materials in which they can be isolated: saliva, plasma, urine, cerebrospinal fluid, bronchial alveolar lavage, and serum [24].…”