Role of Exosomes in Central Nervous System Diseases

Abstract

There are many types of intercellular communication, and extracellular vesicles are one of the important forms of this. They are released by a variety of cell types, are heterogeneous, and can roughly be divided into microvesicles and exosomes according to their occurrence and function. Of course, exosomes do not just play a role in cell-to-cell communication. In the nervous system, exosomes can participate in intercellular communication, maintain the myelin sheath, and eliminate waste. Similarly, exosomes in the brain can play a role in central nervous system diseases, such as stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), prion disease, and traumatic encephalopathy (CTE), with both positive and negative effects (such as the transfer of misfolded proteins). Exosomes contain a variety of key bioactive substances and can therefore be considered as a snapshot of the intracellular environment. Studies have shown that exosomes from the central nervous system can be found in cerebrospinal fluid and peripheral body fluids, and that their contents will change with disease occurrence. Because exosomes can penetrate the blood brain barrier (BBB) and are highly stable in peripheral circulation, they can protect disease-related molecules well and therefore, using exosomes as a biomarker of central nervous system diseases is an attractive prospect as they can be used to monitor disease development and enable early diagnosis and treatment optimization. In this review, we discuss the current state of knowledge of exosomes, and introduce their pathophysiological roles in different diseases of the central nervous system as well as their roles and applications as a viable pathological biomarker.

Cell-to-Cell Communication in Learning and Memory: From Neuro- and Glio-Transmission to Information Exchange Mediated by Extracellular Vesicles

“…Moreover, the ability of EVs, and especially of exosomes, to cross the BBB in both directions is opening the way to use them both in diagnosis [250,273] and therapy [251,287,288]. As discussed, indeed, composition (as well as the amount) of brain-derived circulating EVs can change in brain disorders and in neurodegenerative diseases; in addition, a variety of methods have been developed to load drug molecules of different sizes into them.…”

“…We have, however, to remember that the successful use of EVs in diagnosis depends on the efficacy of the protocols used for their purification from the body fluids and for the analysis of their components; all these steps actually still present some challenges [124,284,285]. In spite of the clear advantages, the use of EVs as drug carriers presents even more challenges because of the fact that EVs are heterogeneous structures that contain hundreds of different proteins (among which are membrane ligands and receptors) and a complex set of both coding and non-coding RNAs, for many of which the functions are not yet clear, and which differ depending on the specific cellular ancestry, as well as the actual physiologic state of the cells [251]. Moreover, in many experiments, in order to obtain high amounts of exosomes, rapidly growing cell lines have been used that might harbour genetic and/or epigenetic modifications leading to secretion of EVs with main/side effects different from the expected ones.…”

“…One peculiar quality of the EVs, and in particular of the exosomes, is their capacity to cross the BBB, so that the analysis of neural-derived exosomes in plasma can give information on CNS status [149,250,251] and might provide biomarkers for different brain pathologies, including mental disorders [136]. On the other hand, it has been suggested that EVs themselves may contribute to alter the integrity of the BBB and to spread diseases and neuroinflammation [252].…”

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

“…EVs are a recognized contributor to neurodegenerative diseases, and both neurotoxic and neuroprotective roles via distribution of EV-mediated cargo, including microRNAs and misfolded proteins, have been implicated [16,17]. In addition, EVs may be usable as a "liquid biopsy" for identification of disease related biomarkers [8,[16][17][18][19][20]. EVs have indeed recently been suggested as putative biomarkers in PD [21].…”

SUMOylation regulates protein cargo in Astrocyte-derived small extracellular vesicles

“…In recent years, sEVs have acquired an important place in the sights of many researchers in the area of neuroscience, due to the fact that they are secreted by most cells, can modulate target cell function (such as neuronal function), are present in the cerebrospinal fluid, and cross the blood brain barrier (Gómez-Molina et al, 2019;Liu et al, 2019). The presence of circulating sEVs in body fluids has opened the possibility that their molecular content could be used as a non-invasive diagnostic strategy to obtain biomarkers of physiological and pathological situations (Lin et al, 2015;Saeedi, Israel, Nagy, & Turecki, 2019;Zhang et al, 2019).…”