Pathogenic extracellular vesicles (EVs)

Pathogenic extracellular vesicles, commonly referred to as toxic exosomes, are small membrane-bound particles (30-150 nm) that serve as critical mediators in the systemic spread of disease-associated molecules [1]. These vesicles are secreted by various cell types and carry a cargo of misfolded proteins, such as amyloid-beta, tau, and alpha-synuclein, which are implicated in the prion-like propagation of neurodegenerative disorders like Alzheimer's and Parkinson's disease [2]. In oncology, toxic exosomes contribute to the remodeling of the pre-metastatic niche and the suppression of the host immune response by transferring oncogenic signals [1]. Therapeutic strategies targeting these vesicles focus on inhibiting their biogenesis through the targeting of enzymes like neutral sphingomyelinase 2 (nSMase2) or blocking the Rab GTPases responsible for vesicle secretion [3]. Additionally, physical removal strategies, such as extracorporeal filtration using lectin-affinity devices, are being explored to clear these pathogenic vesicles from the bloodstream [4]. The primary challenge in targeting toxic exosomes is achieving selectivity, as exosomes also perform essential physiological functions in normal intercellular communication and waste management [1].

Other names

Toxic exosomesPathogenic exosomesDisease-associated exosomesPro-inflammatory extracellular vesiclesProteopathic exosomes

Inhibition of neutral sphingomyelinase 2 (nSMase2) to prevent ceramide-dependent budding; inhibition of Rab GTPases (e.g., Rab27a, Rab27b) to block vesicle docking and fusion; inhibition of the endosomal sorting complex required for transport (ESCRT) machinery; and extracorporeal affinity-based capture and removal from circulation.