Central Nervous System Extracellular Vesicles

Extracellular vesicles (EVs) are complex signaling structures comprised of lipids, proteins and nucleic acids. Since their discovery in the early 1980s, EVs have taken on many names based on their subcellular origin and size. Those formed from budding of the plasma membrane are termed microvesicles, ectosomes, or microparticles and span 100–1,000 nm in diameter, while those secreted via fusion of multivesicular bodies with the plasma membrane are termed exosomes and are generally less than 150 nm in diameter. To date, every cell type studied has been shown to secrete EVs, including all cells of the central nervous system (CNS). In neurons, EVs appear to be released in an activity-dependent manner via a process that may regulate synaptic scaling. Astrocyte-derived EVs have been shown to protect neurons under ischemic conditions and contribute to neuronal plasticity, while EVs secreted by oligodendrocytes provide neuronal axons with trophic support. Collectively, these data suggest very important and diverse capacities for EVs in the brain and warrant further study of the physiological roles EVs and their cargo play in normal CNS function.

Conversely, burgeoning data suggests EVs may contribute to the pathogenesis of several neurological disorders. In diseases typified by protein misfolding and aggregation, EVs have been hypothesized to ‘shuttle’ protein aggregates from neuron to neuron, thereby seeding aggregation in recipient cells. In line with this, EVs have been implicated in the trafficking of the infectious prion protein scrapie (PrPSc), amyloid β-protein, α-synuclein and tau. In addition, EVs have been suggested to modulate neuroinflammatory responses associated with neurodegenerative disease.

Analysis of the contents of EVs from cerebrospinal fluid and blood plasma are being explored as biomarkers for frank and prodromal disease states. With regard to neurodegeneration, most efforts have focused on Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Because EVs provide a potential window into pathological processes occurring in the brain, liquid biopsies offer a unique means to monitor changes in brain-derived biomarkers longitudinally and with minimal invasiveness.

The overarching aim of this Research Topic is to highlight the roles of EVs in CNS function and dysfunction. Authors are encouraged to submit original research on four specific subtopics of CNS EV biology: i) their physiological roles, ii) their involvement in neurodegenerative processes, iii) their use as biomarkers (including technical advancements in methods to isolate EVs from circulating biofluids), and iv) the functions of non-neuronal brain EVs.