Nikolaos Papagiannakis1, Christos Koros2, Maria Stamelou2, Athina-Maria Simitsi2, Matina Maniati3, Roubina Antonelou2, Dimitra Papadimitriou4, Georgia Dermentzaki3, Marina Moraitou5, Helen Michelakakis5, Leonidas Stefanis6. 1. Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 2. 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 3. Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. 4. "Henry Dynan" Hospital, Athens, Greece. 5. Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece. 6. Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: lstefanis@bioacademy.gr.
Abstract
BACKGROUND: Variations of α-synuclein levels or species have been reported in Parkinson's Disease (PD). There has been little systematic examination of erythrocytes, a rich source of α-synuclein. METHODS: Erythrocyte membranes were obtained from PD patients (mutation carriers in the α-synuclein gene (A53T-PD) and glucocerebrosidase gene (GBA-PD) (n=18 each), and patients without known mutations (GU-PD, n=56)), and age-/sex-matched controls (n=56). Levels of monomeric and dimeric α-synuclein were assessed using Western immunoblotting. RESULTS: A statistically significant increase of α-synuclein dimer and dimer to monomer ratio was found in GBA-PD and GU-PD. In contrast, dimer levels of A53T-PD were not different from controls. No difference was found in α-synuclein monomer levels. CONCLUSIONS: The increased α-synuclein dimer in GBA-PD and GU-PD is suggestive of an apparent systemic dysfunction causing the dimerization, and potentially oligomerization, of α-synuclein. These results may have implications for PD pathogenesis and biomarker development.
BACKGROUND: Variations of α-synuclein levels or species have been reported in Parkinson's Disease (PD). There has been little systematic examination of erythrocytes, a rich source of α-synuclein. METHODS: Erythrocyte membranes were obtained from PD patients (mutation carriers in the α-synuclein gene (A53T-PD) and glucocerebrosidase gene (GBA-PD) (n=18 each), and patients without known mutations (GU-PD, n=56)), and age-/sex-matched controls (n=56). Levels of monomeric and dimeric α-synuclein were assessed using Western immunoblotting. RESULTS: A statistically significant increase of α-synuclein dimer and dimer to monomer ratio was found in GBA-PD and GU-PD. In contrast, dimer levels of A53T-PD were not different from controls. No difference was found in α-synuclein monomer levels. CONCLUSIONS: The increased α-synuclein dimer in GBA-PD and GU-PD is suggestive of an apparent systemic dysfunction causing the dimerization, and potentially oligomerization, of α-synuclein. These results may have implications for PD pathogenesis and biomarker development.
Authors: Colleen S Limegrover; Raymond Yurko; Nicholas J Izzo; Kelsie M LaBarbera; Courtney Rehak; Gary Look; Gilbert Rishton; Hank Safferstein; Susan M Catalano Journal: J Neurosci Res Date: 2021-01-22 Impact factor: 4.164
Authors: Lifu Sheng; Tessandra Stewart; Dishun Yang; Eric Thorland; David Soltys; Patrick Aro; Tarek Khrisat; Zhiying Xie; Na Li; Zongran Liu; Chen Tian; Matthew Bercow; Junichi Matsumoto; Cyrus P Zabetian; Elaine Peskind; Joseph F Quinn; Min Shi; Jing Zhang Journal: Acta Neuropathol Commun Date: 2020-07-08 Impact factor: 7.801
Authors: Luis M A Oliveira; Thomas Gasser; Robert Edwards; Markus Zweckstetter; Ronald Melki; Leonidas Stefanis; Hilal A Lashuel; David Sulzer; Kostas Vekrellis; Glenda M Halliday; Julianna J Tomlinson; Michael Schlossmacher; Poul Henning Jensen; Julia Schulze-Hentrich; Olaf Riess; Warren D Hirst; Omar El-Agnaf; Brit Mollenhauer; Peter Lansbury; Tiago F Outeiro Journal: NPJ Parkinsons Dis Date: 2021-07-26