Extracellular vesicle biogenesis and release pathway (EV biogenesis and release)

The extracellular vesicle (EV) biogenesis and release pathway is a complex biological process responsible for the formation and secretion of membrane-bound vesicles, including exosomes and microvesicles, into the extracellular environment. Exosomes originate from the endosomal system through the inward budding of multivesicular bodies (MVBs), a process often regulated by the ESCRT machinery or ceramide-dependent mechanisms, while microvesicles are formed by direct outward budding of the plasma membrane. These vesicles serve as critical mediators of intercellular communication by transporting proteins, lipids, and nucleic acids (such as miRNAs) between cells, thereby influencing various physiological and pathological states. (Source: Nature Reviews Molecular Cell Biology, 2018, doi:10.1038/s41580-018-0004-z). In disease contexts, the EV pathway is frequently hijacked; for instance, cancer cells utilize EVs to promote metastasis, remodel the tumor microenvironment, and confer drug resistance. In neurodegenerative disorders like Alzheimer's and Parkinson's, EVs are implicated in the propagation of proteopathic seeds such as amyloid-beta and alpha-synuclein. Consequently, pharmacological inhibition of EV biogenesis or release using small molecules like GW4869 or DMA is being explored as a therapeutic strategy to halt disease progression. However, because EVs are essential for normal homeostatic functions, achieving cell-type or cargo-specific inhibition remains a significant therapeutic challenge. (Source: Journal of Extracellular Vesicles, 2020, doi:10.1080/20013078.2020.1754111).

Other names

Exosome biogenesis and secretionMicrovesicle formation and sheddingEV secretory pathwayExtracellular vesicle trafficking

Inhibition of neutral sphingomyelinase (nSMase2) to prevent ceramide-dependent budding; inhibition of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery; modulation of Rab GTPases (e.g., Rab27a/b) involved in vesicle docking and fusion; and inhibition of Rho-associated protein kinase (ROCK) to reduce microvesicle shedding.