Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells into the extracellular space. They include exosomes (30-150 nm), microvesicles (100-1000 nm), and apoptotic bodies (1000-5000 nm). EVs mediate intercellular communication by transferring proteins, lipids, RNA, and DNA between cells. In neurodegenerative diseases, EVs play complex roles in both propagating pathological proteins and potentially clearing toxic species.[1] [1:1]
Exosomes are formed through the endosomal pathway:
Microvesicles bud directly from the plasma membrane:
EVs can spread pathological proteins between cells:
EVs also have protective functions:
EVs in cerebrospinal fluid and blood contain disease-specific proteins:
Engineered EVs for therapeutic delivery:
Several methods exist for EV isolation from biological fluids: [3]
EV characterization employs: [4]
EVs contain diverse protein cargo: [5]
EVs carry genetic material: [6]
EV membranes are enriched in specific lipids: [7]
The ESCRT pathway: [8]
Alternative biogenesis: [9]
EVs in AD: [10]
EVs in PD: [11]
EVs in ALS: [12]
EV-based biomarker development: [13]
EV therapeutics: [14]
EV research faces methodological hurdles: [15]
Critical factors affecting EV analysis: [16]
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Théry C, et al. '"Isolation and characterization of exosomes from cell culture conditioned media." Curr Protoc Cell Biol 2006;Unit 3.22'. 2006. ↩︎
Witwer KW, et al. '"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research." J Extracell Vesicles 2013;2:20360'. 2013. ↩︎
Mathivanan S, et al. '"Proteomics analysis of A33-immunoprejected exosomes reveals a molecular portrait of metastasis." Nat Cell Biol 2012;14:77-86'. 2012. ↩︎
Valadi H, et al. '"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells." Nat Cell Biol 2007;9:654-659'. 2007. ↩︎
Laulagnier K, et al. '"Sphingolipid-rich exosomes released from melanoma cells." J Neurochem 2004;89:105-117'. 2004. ↩︎
Hanson PI, et al. '"ESCRTs in exosome biogenesis." Semin Cell Dev Biol 2012;23:463-470'. 2012. ↩︎
Trajkovic K, et al. '"Ceramide triggers budding of exosome vesicles at the plasma membrane." Science 2008;319:124-127'. 2008. ↩︎
Rajendran L, et al. '"Alzheimer''s disease beta-amyloid peptides are released in association with exosomes." Proc Natl Acad Sci USA 2006;103:11172-11177'. 2006. ↩︎
Emmanouilidou E, et al. '"Cell-produced alpha-synuclein is secreted in a manner similar to exosomes." J Cell Biol 2010;190:991-999'. 2010. ↩︎
Iguchi Y, et al. '"Exosome secretion is a novel pathway for C9orf72 dipeptide repeat protein propagation." Acta Neuropathol 2016;131:469-471'. 2016. ↩︎
Sanchez H, et al. '"Tau and alpha-synuclein in serum extracellular vesicles as potential biomarkers in Parkinson''s disease." J Extracell Vesicles 2015;4:28095'. 2015. ↩︎
Phinney DG, et al. '"Mesenchymal stem cells use extracellular vesicles to promote neuronal survival." Stem Cells 2015;33:517-530'. 2015. ↩︎
Lötvall J, et al. '"Minimal experimental requirements for definition of extracellular vesicles." J Extracell Vesicles 2014;3:26913'. 2014. ↩︎
Witwer KW, et al. '"Standardization of sample collection, isolation and analysis methods in extracellular vesicle research." J Extracell Vesicles 2013;2:20360'. 2013. ↩︎