Papagiannakis Nikolaos, Koros Christos, Stamelou Maria, Simitsi Athina-Maria, Maniati Matina, Antonelou Roubina, Papadimitriou Dimitra, Dermentzaki Georgia, Moraitou Marina, Michelakakis Helen, Stefanis Leonidas
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.
2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Neurosci Lett. 2018 Apr 13;672:145-149. doi: 10.1016/j.neulet.2017.11.012. Epub 2017 Nov 10.
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.
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.
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.
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.
帕金森病（PD）患者中已报道了α-突触核蛋白水平或种类的变化。对富含α-突触核蛋白的红细胞进行的系统检查较少。
从PD患者（α-突触核蛋白基因（A53T-PD）和葡萄糖脑苷脂酶基因（GBA-PD）的突变携带者（各18例）以及无已知突变的患者（GU-PD，56例））和年龄/性别匹配的对照者（56例）中获取红细胞膜。使用Western免疫印迹法评估单体和二聚体α-突触核蛋白的水平。
在GBA-PD和GU-PD中发现α-突触核蛋白二聚体以及二聚体与单体的比例有统计学意义的增加。相比之下，A53T-PD的二聚体水平与对照无差异。α-突触核蛋白单体水平未发现差异。
GBA-PD和GU-PD中α-突触核蛋白二聚体增加提示存在明显的全身性功能障碍，导致α-突触核蛋白二聚化并可能寡聚化。这些结果可能对PD发病机制和生物标志物开发有影响。
