机构：[1]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China首都医科大学宣武医院[2]Department of Human Anatomy, School of Basic Medical Sciences, Beihua University, Jilin, China[3]Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China[4]Beijing Key Laboratory for Parkinson’s Disease, Beijing, China
A pathological hallmark of Parkinson's disease (PD) is formation of Lewy bodies in neurons of the brain. This has been attributed to the spread of alpha-synuclein (alpha-syn) aggregates, which involves release of alpha-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more alpha-syn phosphorylation and oligomerization than plasma from normal subjects (NS). Compared with NS plasma, PD plasma added to primary neuron cultures caused more cell death in the presence of extracellular alpha-syn. This was supported by the observations that phosphorylated alpha-syn oligomers entered neurons, rapidly increased accumulated thioflavin S-positive inclusions, and induced a series of metabolic changes that included activation of polo-like kinase 2, inhibition of glucocerebrosidase and protein phosphatase 2A, and reduction of ceramide levels, all of which have been shown to promote alpha-syn phosphorylation and aggregation. We also analyzed neurotoxicity of alpha-syn oligomers relative to plasma from different patients. Neurotoxicity was not related to age or gender of the patients. However, neurotoxicity was positively correlated with H&Y staging score. The modification in the plasma may promote spreading of alpha-syn aggregates via an alternative pathway and accelerate progression of PD.
基金：
the Natural Science Foundation of China (Grant nos. 81371200, 81401042, and 81071014),
the National Basic Research Program (“973”Program) of China (Grant no. 2011CB504101),
the National Science and Technology Support Program (Grant no.2012BAI10B03),
the National High Technology Research and Development Program (“863” Program) of China (Grant no.2006AA02A408),
Special Scientific Research Funds for Capital Health Development (Grant no. 2011-1001-01).
第一作者机构：[1]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China[2]Department of Human Anatomy, School of Basic Medical Sciences, Beihua University, Jilin, China
通讯作者：
通讯机构：[1]Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China[3]Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China[4]Beijing Key Laboratory for Parkinson’s Disease, Beijing, China
推荐引用方式(GB/T 7714)：
Peng Wang ,Xin Li ,Xuran Li ,et al.Blood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity[J].PARKINSONS DISEASE.2016,2016:doi:10.1155/2016/7596482.
APA：
Peng Wang,,Xin Li,,Xuran Li,,Weiwei Yang,&Shun Yu.(2016).Blood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity.PARKINSONS DISEASE,2016,
MLA：
Peng Wang,,et al."Blood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity".PARKINSONS DISEASE 2016.(2016)
