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Cryo-electron microscopy of plasma extracellular vesicles in lysosomal storage diseases
https://doi.org/10.25557/2073-7998.2025.06.72-74
Abstract
Lysosomal storage diseases (LSD) are a group of rare disorders caused by impaired lysosomal function, characterized by a deficiency in the activity of lysosomal enzymes and accumulation of their substrates. It is assumed that cells can facilitate the accumulation of substrates through exocytosis and changes in extracellular vesicle (EV) biogenesis, leading to changes in their morphology and size. EVs are membrane objects less than 1000 nm in size that perform various biological functions, such as the transport of biologically active molecules (proteins, lipids, microRNAs, mRNAs, and DNA) and intercellular interaction. The role of these objects in health and disease is actively being studied for potential use as biomarkers or therapeutic purposes. Objective: to evaluate the morphology and size of plasma EVs in LSD using cryo-electron microscopy. The study included patients with LSD, including patients with Gaucher disease, Fabry disease, Niemann-Pick disease and controls. EVs were isolated from blood plasma samples using ultracentrifugation. For the first time, the morphology and size of plasma EVs in patients with LSD were characterized using cryo-electron microscopy. Based on the results of analysis, it was found that the plasma EVs of LSD patients are characterized by complications in vesicle morphology, as well as the presence of electron-dense cargo. Plasma EVs from a patient receiving substrate-reducing therapy for Gaucher disease are also characterized by an increase in vesicle size compared to controls. Our results indicate changes in the biogenesis and composition of blood plasma EVs in LSD.
Keywords
Lysosomal storage diseases,
extracellular vesicles,
cryo-electron microscopy,
Gaucher disease,
Fabry disease,
Niemann-Pick disease
Supporting agencies: The study was supported by the Russian Science Foundation grant 19-74-20146-п.
About the Authors
A. E. Kopytova
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
Alena E. Kopytova.
1, mkr. Orlova roshcha, Gatchina, 188300; 6/8 L’va Tolstogo st. St. Petersburg, 197022
A. D. Izyumchenko
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300; 6/8 L’va Tolstogo st. St. Petersburg, 197022
L. А. Garaeva
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300
A. V. Artynyuk
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300
V. A. Bezrukikh
Almazov National Medical Research Centre
Russian Federation
Russian Federation
2, Akkuratova st., St. Petersburg, 197341
E. B. Pichkur
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»;National Research Center «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300; 1, Akademika Kurchatov Square, Moscow, 123182
A. L. Konevega
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»;National Research Center «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300; 1, Akademika Kurchatov Square, Moscow, 123182
T. A. Shtam
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»;National Research Center «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300; 1, Akademika Kurchatov Square, Moscow, 123182
S. N. Pchelina
Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Center «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
1, mkr. Orlova roshcha, Gatchina, 188300; 6/8 L’va Tolstogo st. St. Petersburg, 197022
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Review
For citations:
Kopytova A.E., Izyumchenko A.D., Garaeva L.А., Artynyuk A.V., Bezrukikh V.A., Pichkur E.B., Konevega A.L., Shtam T.A., Pchelina S.N. Cryo-electron microscopy of plasma extracellular vesicles in lysosomal storage diseases. Medical Genetics. 2025;24(6):72-74. (In Russ.) https://doi.org/10.25557/2073-7998.2025.06.72-74
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