title: Increased plasma oligomeric alpha-synuclein in patients with lysosomal storage diseases.
abstract: A link between lysosomal storage diseases (LSDs) and neurodegenerative disorders associated with accumulation of presynaptic protein alpha-synuclein has been shown. Particularly, Gaucher disease (GD) patients with a deficiency of the lysosomal enzyme glucocerebrosidase (GBA) and carriers of GBA mutations are at increased risk of Parkinson's disease (PD). It remains unclear whether this link is due to increased alpha-synuclein oligomerization. Here we show that level of oligomeric alpha-synuclein form, associated with PD development, is increased in plasma of GD patients (n=41, median=22.9pg/mL, range1.57-444.58pg/mL; controls (n=40, median=6.02pg/mL, range 1.05-103.14pg/mL, p<0.0001). This difference is absent in GD patients receiving enzyme replacement therapy (ERT) for more than 5 years. Moreover, the levels of alpha-synuclein oligomers in plasma are also higher in patients with other LSDs (Niemann-Pick type C, Krabbe disease, Wolman disease) compared to the median value in controls. Therefore, we suggest that mutations in the GBA gene and at least in several other LSDs genes may be associated with an increase in oligomeric alpha-synuclein in plasma. ERT applied for recovering of GBA functions in GD treatment might decrease formation of plasma oligomeric alpha-synuclein.
authors.affiliation: Petersburg Nuclear Physics Institute, St. Petersburg, Russia; First Pavlov's State Medical University of Saint-Petersburg, St. Petersburg, Russia; St. Petersburg Academic University - Nanothecnology Research and Education Centre, RAS, St. Petersburg, Russia. Electronic address: sopchelina@hotmail.com.
authors.forename: S N
authors.initials: SN
authors.lastname: Pchelina
authors.affiliation: First Pavlov's State Medical University of Saint-Petersburg, St. Petersburg, Russia.
authors.forename: E P
authors.initials: EP
authors.lastname: Nuzhnyi
authors.affiliation: Petersburg Nuclear Physics Institute, St. Petersburg, Russia; First Pavlov's State Medical University of Saint-Petersburg, St. Petersburg, Russia; St. Petersburg Academic University - Nanothecnology Research and Education Centre, RAS, St. Petersburg, Russia.
authors.forename: A K
authors.initials: AK
authors.lastname: Emelyanov
authors.affiliation: Medical-genetics Scientific Center, Moscow, Russia.
authors.forename: T M
authors.initials: TM
authors.lastname: Boukina
authors.affiliation: Petersburg Nuclear Physics Institute, St. Petersburg, Russia; First Pavlov's State Medical University of Saint-Petersburg, St. Petersburg, Russia.
authors.forename: T S
authors.initials: TS
authors.lastname: Usenko
authors.affiliation: Petersburg Nuclear Physics Institute, St. Petersburg, Russia; St. Petersburg Academic University - Nanothecnology Research and Education Centre, RAS, St. Petersburg, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Nikolaev
authors.affiliation: First Pavlov's State Medical University of Saint-Petersburg, St. Petersburg, Russia.
authors.forename: G N
authors.initials: GN
authors.lastname: Salogub
authors.affiliation: First Pavlov's State Medical University of Saint-Petersburg, St. Petersburg, Russia.
authors.forename: A F
authors.initials: AF
authors.lastname: Yakimovskii
authors.affiliation: Medical-genetics Scientific Center, Moscow, Russia.
authors.forename: E Yu
authors.initials: EY
authors.lastname: Zakharova
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D006801:Humans; D007223:Infant; D016464:Lysosomal Storage Diseases / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D051844:alpha-Synuclein / Q000097:blood*
chemical_list: D051844:alpha-Synuclein
keywords: Alpha-synuclein; Gaucher disease; Lysosomal storage diseases; Oligomerization; Parkinson's disease