Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity
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 α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plas...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
|
| Series: | Parkinson's Disease |
| Online Access: | http://dx.doi.org/10.1155/2016/7596482 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562787019128832 |
|---|---|
| author | Peng Wang Xin Li Xuran Li Weiwei Yang Shun Yu |
| author_facet | Peng Wang Xin Li Xuran Li Weiwei Yang Shun Yu |
| author_sort | Peng Wang |
| collection | DOAJ |
| description | 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 α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-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 α-syn. This was supported by the observations that phosphorylated α-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 α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-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 α-syn aggregates via an alternative pathway and accelerate progression of PD. |
| format | Article |
| id | doaj-art-11fd01077ccd4c5690605d4827945d1c |
| institution | Kabale University |
| issn | 2090-8083 2042-0080 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Parkinson's Disease |
| spelling | doaj-art-11fd01077ccd4c5690605d4827945d1c2025-02-03T01:21:48ZengWileyParkinson's Disease2090-80832042-00802016-01-01201610.1155/2016/75964827596482Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and NeurotoxicityPeng Wang0Xin Li1Xuran Li2Weiwei Yang3Shun Yu4Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, ChinaDepartment of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, ChinaDepartment of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, ChinaDepartment of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, ChinaDepartment of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, ChinaA 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 α-synuclein (α-syn) aggregates, which involves release of α-syn from a neuron and its reuptake by a neighboring neuron. We found that treatment with plasma from PD patients induced more α-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 α-syn. This was supported by the observations that phosphorylated α-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 α-syn phosphorylation and aggregation. We also analyzed neurotoxicity of α-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 α-syn aggregates via an alternative pathway and accelerate progression of PD.http://dx.doi.org/10.1155/2016/7596482 |
| spellingShingle | Peng Wang Xin Li Xuran Li Weiwei Yang Shun Yu Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity Parkinson's Disease |
| title | Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity |
| title_full | Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity |
| title_fullStr | Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity |
| title_full_unstemmed | Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity |
| title_short | Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity |
| title_sort | blood plasma of patients with parkinson s disease increases alpha synuclein aggregation and neurotoxicity |
| url | http://dx.doi.org/10.1155/2016/7596482 |
| work_keys_str_mv | AT pengwang bloodplasmaofpatientswithparkinsonsdiseaseincreasesalphasynucleinaggregationandneurotoxicity AT xinli bloodplasmaofpatientswithparkinsonsdiseaseincreasesalphasynucleinaggregationandneurotoxicity AT xuranli bloodplasmaofpatientswithparkinsonsdiseaseincreasesalphasynucleinaggregationandneurotoxicity AT weiweiyang bloodplasmaofpatientswithparkinsonsdiseaseincreasesalphasynucleinaggregationandneurotoxicity AT shunyu bloodplasmaofpatientswithparkinsonsdiseaseincreasesalphasynucleinaggregationandneurotoxicity |