title: Blood Plasma of Patients with Parkinson's Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity.
abstract: 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 ofα-synuclein (α-syn) aggregates, which involves release ofα-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced moreα-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 extracellularα-syn. This was supported by the observations that phosphorylatedα-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 promoteα-syn phosphorylation and aggregation. We also analyzed neurotoxicity ofα-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 ofα-syn aggregates via an alternative pathway and accelerate progression of PD.
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Human Anatomy, School of Basic Medical Sciences, Beihua University, Jilin, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: Xuran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, China; Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory for Parkinson's Disease, Beijing, China.
authors.forename: Shun
authors.identifier: 0000-0002-2591-9764
authors.initials: S
authors.lastname: Yu