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Plasma Exosomes in Inherited Forms of Parkinson’s Disease

Authors
  • Kulabukhova, D. G.1, 2
  • Garaeva, L. A.1, 3
  • Emelyanov, A. K.1, 2
  • Senkevich, K. A.1, 2
  • Gracheva, E. V.4
  • Miliukhina, I. V.1, 2, 4
  • Varfolomeeva, E. Y.1, 3
  • Timofeeva, A. A.2
  • Schwartsman, A. L.1
  • Shtam, T. A.1, 3
  • Pchelina, S. N.1, 2, 3, 4
  • 1 Konstantinov Petersburg Nuclear Physics Institute, National Research Center Kurchatov Institute, Gatchina, 188300, Russia , Gatchina (Russia)
  • 2 First Pavlov State Medical University of St. Petersburg, St. Petersburg, 197022, Russia , St. Petersburg (Russia)
  • 3 National Research Center “Kurchatov Institute”, Moscow, 123182, Russia , Moscow (Russia)
  • 4 Institute of Experimental Medicine, St. Petersburg, 197376, Russia , St. Petersburg (Russia)
Type
Published Article
Journal
Molecular Biology
Publisher
Pleiades Publishing
Publication Date
Mar 01, 2021
Volume
55
Issue
2
Pages
297–303
Identifiers
DOI: 10.1134/S002689332101009X
Source
Springer Nature
Keywords
License
Yellow

Abstract

AbstractParkinson’s disease (PD) is the second most common neurodegenerative disorder. Alpha-synuclein misfolding and aggregation resulting in neurototoxicity is a hallmark of PD. The prion properties of alpha-synuclein are still under discussion. Exosomes (extrcellular vesicles 40–100 nm in size) can play a key role in the transport of pathogenic forms of alpha-synuclein. The most frequent inherited forms of the disease are PD associated with mutation in the leucine-rich repeat kinase 2 (LRRK2-PD) and glucocerebrosidase (GBA-PD) genes. The aim of our work is to evaluate the concentration and size of exosomes derived from blood plasma of patients with GBA-PD, asymptomatic GBA mutation carriers, and the effect of GBA and LRRK2 mutations on alpha-synuclein level in exosomes derived from peripheral blood plasma. Plasma extracellular vesicles were isolated via chemical precipitation and sequential ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis (NTA), and flow cytometry. Total alpha-synuclein level in plasma exosomes was estimated by enzyme-linked immunosorbent assay. Patients with sporadic PD, PD with dementia, patients with inherited PD (GBA-PD, LRRK2-PD), and GBA mutation carriers were included in the study. The concentration on plasma exosomes was higher in GBA-PD patients that in sporadic PD patients, asymptomatic carriers of mutations on GBA gene, and control (p = 0.004, 0.019 and 0.0001 respectively). The size of plasma exosomes was higher in GBA-PD patients compared to asymptomatic carriers of GBA mutations and control (p = 0.009 and 0.0001, respectively). No significant difference was found for exosomal alpha-synuclein levels in the studied groups. Our results allowed us to suggest that a decrease in GBA activity may affect the pool of plasma exosomes, and mutations in the LRRK2 and GBA genes do not influence the level of plasma exosomal alpha-synuclein.

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