Prion protein fragment (106–126) induces prothrombotic state by raising platelet intracellular calcium and microparticle release

Inhibiting extracellular vesicles formation and release: a review of EV inhibitors

“…µ-and m-calpains are hetero-dimers consisting of a large catalytic subunit (80 Cystein proteinase inhibitors Calpains, involved in MVs production. Concentrations used: 0-300 µM in vitro 10 mg/Kg of body weight in vivo [52][53][54][55][56]58] Manumycin A [63][64][65][66][67] (Continued ) [35,74,75] 20 mg/Kg of body weight in vivo [102] GW4869 [34,38,62,[76][77][78][79][80][81][82][83][84][85][86] IUPAC = International Union of Pure and Applied Chemistry.…”

“…In a subsequent experiment, Yano et al [55] showed the calpeptin activity to be concentration dependent (0-300 µM) and that the reduction of MVs shedding is mostly due to the reduced activity of calpain on actin-binding proteins, as the inhibition of MVs formation was observed 10 min after platelets incubation with thrombin and collagen. Platelets [52] Microparticles No isolation FACS analysis with Annexin V and CD41a Platelets [53] Microparticle Differential centrifugation FACS analysis with Annexin V and CD41a Platelets [54] Microvesicles (a) 0.2 µm filtration (b) Ultracentrifugation Radio-labelled membrane glycoprotein quantification Platelets [55] Microparticles No isolation FACS analysis for GP IIb-IIIa and GP Ib HEK293, SH-SY5Y [56] Microvesicles Ultracentrifugation Live-cell confocal microscopy and FACS with Annexin A1 PC3 [58] Microvesicles Differential centrifugation NTA, TEM and FACS analysis with Annexin V F11, HeLa, rat dorsal root ganglion, mouse neuroblastoma hybrid cells [60] Exosomes Differential ultracentrifugation NTA, Immunoblots for: Tsg101, CD63…”

Glutamate induces synthesis of thrombogenic peptides and extracellular vesicle release from human platelets

“…We have recently reported pro-thrombotic attributes of amyloidogenic neurotoxic peptides like amyloid beta and prion protein 13,14 . In the present study we demonstrate that, glutamate switches human platelets to pro-activation phenotype as reflected from synthesis of thrombogenic peptides from pre-existing mRNAs, activation of RhoA-Rho kinase-myosin light chain (MLC) signalling axis, extensive shedding of extracellular vesicles (EVs), augmented spreading on immobilized matrix, and formation of large platelet microthrombi under arterial shear.…”

Inhibiting Extracellular Vesicle Trafficking as Antiviral Approach to Corona Virus Disease 2019 Infection

“…Calpeptin blocks calpains, a family calcium-dependent cysteine proteases involved in different cellular processes including microvesicles shedding. Calpeptin has been demonstrated to reduce microvesicle production by activated platelets (Fox et al, 1991;Crespin et al, 2009;Mallick et al, 2015), HEK293 cells (Atanassoff et al, 2014), and PC3 cell line (Jorfi et al, 2015), and to be effective in inhibiting Severe Acute Respiratory Syndrome-Associated Coronavirus (SARSCoV) replication in vitro (Barnard et al, 2004).…”