Emerging Roles of Extracellular Vesicles in the Central Nervous System: Physiology, Pathology, and Therapeutic Perspectives

Abstract

Extracellular vesicles or EVs are secreted by most, if not all, eukaryote cell types and recaptured by neighboring or distant cells. Their cargo, composed of a vast diversity of proteins, lipids, and nucleic acids, supports the EVs’ inter-cellular communication. The role of EVs in many cellular processes is now well documented both in physiological and pathological conditions. In this review, we focus on the role of EVs in the central nervous system (CNS) in physiological as well as pathological conditions such as neurodegenerative diseases or brain cancers. We also discuss the future of EVs in clinical research, in particular, their value as biomarkers as well as innovative therapeutic agents. While an increasing number of studies reveal EV research as a promising field, progress in the standardization of protocols and innovation in analysis as well as in research tools is needed to make a breakthrough in our understanding of their impact in the pathophysiology of the brain.

The Multifaceted Role of Extracellular Vesicles in Glioblastoma: microRNA Nanocarriers for Disease Progression and Gene Therapy

“…EVs represent an integral part in the physiology of different tissues and organs, including the CNS, with roles in neurodevelopment, neuroprotection, differentiation and signaling [ 130 ]. In pathological states, activated or malignant cells release EVs which maintain and exacerbate disease-related processes, such as proliferation, migration and invasion of cancer cells, angiogenesis, metastasis, resistance to apoptosis, immune escape, inflammation, etc.…”

“…[ 113 ]. GB cells release EVs, which carry oncogenic factors and act as mediators in intercellular communication, leading to the formation of a pro-tumorigenic environment [ 130 , 131 ]. It is clear that EVs promote horizontal malignancy in GB, by transferring their cargo to neighboring cells, inducing tumor-supportive phenotypes, promoting angiogenesis and immunosuppression, increasing proliferation, modulating metabolic activity and conferring drug resistance [ 132 , 133 ].…”

Nanosystems and exosomes as future approaches in treating multiple sclerosis

“…As reported, bidirectional communication between glial cells and neurons via exosomes underlies also a complex processes which are myelination/remyelination (Bavisotto et al, 2019;Gassama & Favereaux, 2021;Li, Luo, et al, 2019). The mature oligodendrocytes release exosomes as a result of neuronal electrical activity in response to the neurotransmitter glutamate upon activation of glial ionotropic glutamate receptors (Frühbeis et al, 2013).…”

“…Being involved in intercellular communication, exosomes influence biological processes such as cell differentiation, regulate synaptic activity and biogenesis of myelin (Gassama et al, 2021). Exosomes are also crucial in immune stimulation and tolerance due to their involvement in immune signalling and inflammation (Bobrie et al, 2011).…”

Brain-Derived Exosomal Proteins as Effective Biomarkers for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

“…Glial and neuronal cell populations both release extracellular vesicles (EVs) that contain cargos of proteins such as transmembrane proteins, and lipids, RNAs, mitochondrial DNA, and single-stranded and double-stranded DNA [18]. The EVs mainly comprise exosomes ranging from a diameter of 30-140 nm, microvesicles (MVs) ranging from 100-1000 nm, and apoptotic bodies ranging from 100-5000 nm [19][20][21]. Although MVs are generated from budding of the cell membrane, they might be potential diagnostic biomarkers as they can be distinguished from other exosomes by their size and the mechanisms involved in their generation [22,23].…”