**Author details**

*Extracellular Vesicles and Their Importance in Human Health*

type, or condition specific [121].

our ability to capitalize on this natural social network.

recycling in the neuronal synapse to organ development and ion homeostasis [25]. Many of the common, well-known endocytosis receptors utilize clathrin coated pits, such as low-density lipoprotein receptor (LDLR) and transferrin receptor (TfR). One of the most commonly used ways to determine which of these mechanisms is in operation is through inhibitory drugs or knocking down certain key players [121]. Dynamin, a GTPase, facilitates the fission of the intracellular clathrin coated vesicle [25, 123]. Dynasore, an inhibitor of dynamin, has been utilized to effectively block endocytosis of extracellular vesicles and establish clathrin-mediated endocytosis as a mechanism of uptake for these vesicles [21, 52, 56]. Following siRNA downregulation of caveolin-1 (the primary protein involved in caveolae-dependent endocytosis), exosome internalization was significantly reduced in B cells [95, 121]. Inhibitory drugs have also been useful in the determination of a third mechanism, lipid-raft mediated endocytosis. The lipid raft is a small portion of the plasma membrane, rich in sphingolipids and sterols, that facilitates various cellular processes [124]. Use of methyl-β-cyclodextrin (MβCD), which alters the cholesterol content of the membrane and disrupts lipid rafts, has been seen by several groups to impair exosomal internalization [43, 44, 97]. While lipid raft-dependent endocytosis is the primary clathrin- and caveolaeindependent mechanism, other pathways and independent interactions have been described in the internalization of exosomes [61, 124]. Endocytosis is the primary method of exosomal delivery of its contents but research is still needed to understand what determines the specific mechanism whether it is cell type, exosome

Exosome stability, ubiquitous presence, and influential contents make them ideal candidates for therapeutic modalities in a wide variety of pathologies. The significance of exosomal contribution to the cellular network throughout the body still carries untapped potential for conquering some of the most pressing current health challenges including cancer and neurodegeneration. Understanding how these exosomes interact with and enter the myriad of cells in the body will empower

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Amber Gonda1,2†, Ron Moyron1,3†, Janviere Kabagwira1,3†, Paul A. Vallejos1† and Nathan R. Wall1,3\* †

1 Center for Health Disparities & Molecular Medicine, Loma Linda, CA, USA

2 Department of Pathology and Anatomy, Loma Linda, CA, USA

3 Division of Biochemistry, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA

\*Address all correspondence to: nwall@llu.edu

† All authors contributed to the design of this review, while AG, RM, PV and JK drafted the manuscript. AG, RM, and NRW revised and finalized the manuscript.

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
