title: Extracellular vesicles as modulators of cell-to-cell communication in the healthy and diseased brain.
abstract: Homeostasis relies heavily on effective cell-to-cell communication. In the central nervous system (CNS), probably more so than in other organs, such communication is crucial to support and protect neurons especially during ageing, as well as to control inflammation, remove debris and infectious agents. Emerging evidence indicates that extracellular vesicles (EVs) including endosome-derived exosomes and fragments of the cellular plasma membrane play a key role in intercellular communication by transporting messenger RNA, microRNA (miRNA) and proteins. In neurodegenerative diseases, secreted vesicles not only remove misfolded proteins, but also transfer aggregated proteins and prions and are thus thought to perpetuate diseases by 'infecting' neighbouring cells with these pathogenic proteins. Conversely, in other CNS disorders signals from stressed cells may help control inflammation and inhibit degeneration. EVs may also reflect the status of the CNS and are present in the cerebrospinal fluid indicating that exosomes may act as biomarkers of disease. That extracellular RNA and in particular miRNA, can be transferred by EV also indicates that these vesicles could be used as carriers to specifically target the CNS to deliver immune modulatory drugs, neuroprotective agents and anti-cancer drugs. Here, we discuss the recent evidence indicating the potential role of exosomes in neurological disorders and how knowledge of their biology may enable a Trojan-horse approach to deliver drugs into the CNS and treat neurodegenerative and other disorders of the CNS.
authors.affiliation: Exosomes Research Group, VU University Medical Center, 1007 MB Amsterdam, The Netherlands d.pegtel@vumc.nl.
authors.forename: D M
authors.initials: DM
authors.lastname: Pegtel
authors.affiliation: Neuropathology, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Peferoen
authors.affiliation: Neuropathology, Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands Neuroimmunology Unit, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors.forename: S
authors.initials: S
authors.lastname: Amor
mesh_terms: D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods; D055354:Exosomes / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*
keywords: drug delivery; exosomes; extracellular vesicles; neurodegeneration; therapy