Abstract
The central nervous system (CNS) consists of a heterogeneous population of cells with highly specialized functions. For optimal functioning of the CNS, in disease and in health, intricate communication between these cells is vital. One important mechanism of cellular communication is the release and uptake of extracellular vesicles (EVs). EVs are membrane enclosed particles actively released by cells, containing a wide array of proteins, lipids, RNA, and DNA. These EVs can be taken up by neighboring or distant cells, and influence a wide range of processes. Due to the complexity and relative inaccessibility of the CNS, our current understanding of the role of EVs is mainly derived in vitro work. However, recently new methods and techniques have opened the ability to study the role of EVs in the CNS in vivo. In this review, we discuss the current developments in our understanding of the role of EVs in the CNS in vivo.
Highlights
The central nervous system (CNS) consists of a heterogeneous population of cells, all functioning in a distinct milieu protected by the skull and blood–brain barrier (BBB)
extracellular vesicles (EVs) are distinctly different from synaptic vesicles, the contents of which are released by exocytosis and the role of which is strictly tied to the signaling by neurotransmitters and neuropeptides between neurons at synapses [6,7]
Loss of dopaminergic neurons in substantia nigra and the presence of α-syn aggregates in Lewy bodies in the brain are key factors in Parkinson’s disease (PD), causing loss of voluntary movements with rigidity, tremors, and bradykinesia in PD patients [44,45]. α-Syn oligomers can propagate through neurons in a prion-like manner, exacerbating neurodegeneration [46]. α-Syn is endocytosed via the ‘Endosomal Sorting Complexes Required for Transport’ (ESCRT) pathway and transported for degradation to multivesicular bodies (MVBs) [47]
Summary
The central nervous system (CNS) consists of a heterogeneous population of cells, all functioning in a distinct milieu protected by the skull and blood–brain barrier (BBB). Interference in cell-to-cell communication in the brain can have a role in initiating various disease processes (e.g., neurodegeneration) and can be hijacked by tumors to hinder an adequate (inflammatory/immune) response [1,2]. Extracellular vesicles (EVs) are membrane enclosed structures, typically 30 to 500 nm in diameter, originating from multivesicular bodies (MVBs) or plasma membrane [3]. These particles are naturally released from cells and contain nucleic acids, peptides/proteins, lipids, and other cellular constituents [3,4]. Use of EVs as biomarkers detected in blood [18] or cerebrospinal fluid (CSF) is beyond the scope of this review and will not be discussed [19]
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