title: α-Synuclein dimerization in erythrocytes of Gaucher disease patients: correlation with lipid abnormalities and oxidative stress.
abstract: Several observations suggest that disturbed homeostasis of α-Synuclein (α-Syn) may provide a link between Gaucher disease (GD) and Parkinson's disease (PD). We recently reported increased dimerization of α-Syn in the red blood cell (RBC) membrane of patients with GD. Several studies indicate a crucial relationship between lipids, oxidative stress and α-Syn status. Here we investigated the relationship between the observed increased dimerization of α-Syn in the cell membranes of RBCs, cells devoid of lysosomes and lacking lysosomal enzyme synthesis, and the lipid abnormalities and oxidative stress already described in GD. Correlation studies showed that in GD the α-Syn dimer/monomer ratio is positively correlated with the levels of glucosylceramide (GlcCer) and the glucosylceramide/ceramide (GlcCer/Cer) ratio and negatively with the levels of malonyldialdehyde (MDA) and plasmalogens. In conclusion, we have shown that the increased tendency of α-Syn to form dimers in the RBC membrane of patients with GD, is correlated with both the level of lipids, including GlcCer, the primary lipid abnormality in GD, and the increased oxidative stress observed in this disorder. The study of other tissues, and in particular brain, will be important in order to elucidate the significance of these findings regarding the link between GD and PD.
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Moraitou
authors.affiliation: Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Dermentzaki
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Dimitriou
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Monopolis
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Nick
authors.initials: N
authors.lastname: Dekker
authors.affiliation: Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Aerts
authors.affiliation: Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Second Department of Neurology, National and Kapodistrian University of Athens Medical School, Athens, Greece.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stefanis
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece. Electronic address: inchildh@otenet.gr.
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002518:Ceramides / Q000097:blood; D002675:Child, Preschool; D019281:Dimerization; D004912:Erythrocytes / Q000378:metabolism*; D005776:Gaucher Disease / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D010955:Plasmalogens / Q000097:blood; D055815:Young Adult; D051844:alpha-Synuclein / Q000097:blood* / Q000737:chemistry
chemical_list: D002518:Ceramides; D008055:Lipids; D010955:Plasmalogens; D051844:alpha-Synuclein; D008315:Malondialdehyde
keywords: Gaucher disease; Glucosylceramide; Oxidative stress; Parkinson’s disease; Plasmalogens; ɑ-Synuclein