Blood plasma of patients with Parkinson's disease increases alpha-synuclein neurotoxicity and its mechanisms

doi:10.3969/j.issn.1006-7795.2019.02.017

Abstract

Abstract: Objective To investigate the effect of plasma of Parkinson's disease (PD) on the cytotoxicity of α-synuclein (α-Syn) and its mechanism. Methods Recombinant human α-Syn was added to PD and normal subject plasma. Western blotting and ELISA method were used to identify α-Syn oligomers and phosphorylation. Add α-Syn monomer and oligomer at a final concentration of 5μM to primary neuronal medium with 30% PD plasma, normal subject plasma and fetal bovine plasma, after 14 days of incubation, MTT and flow cytometry were used to observe the cell death. Enzyme activity kit was used to detect the activity of protein phosphatase 2A (PP2A) enzyme in primary neurons of each group. Results Plasma in PD patients induced more α-Syn phosphorylation and oligomerization than normal subjects (NS) plasma. Compared to NS plasma, PD plasma added to primary neuronal cultures resulted in more cells dying in the presence of extracellular α-Syn, accompanied by decreased protein phosphatase 2A activity. Conclusion The plasma of PD patients may phosphorylate α-Syn by decreasing the activity of PP2A enzyme, leading to aggregation and further death of primary cultured neurons.

Key words: α-synuclein, plasma, Parkinson's disease, neurons, phosphorylation

CLC Number:

R742

Li Jie, Xie Xiujuan, Song Wei, Pan Weihua, Yang Weiwei, Yu Shun. Blood plasma of patients with Parkinson's disease increases alpha-synuclein neurotoxicity and its mechanisms[J]. Journal of Capital Medical University, 2019, 40(2): 244-250.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.02.017

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I2/244

References

[1] Obeso J A, Stamelou M, Goetz C G, et al. Past, present, and future of parkinson's disease:a special essay on the 200th anniversary of the shaking palsy[J]. Mov Disord, 2017, 32(9):1264-1310.
[2] Braak H, Ghebremedhin E, Rub U, et al. Stages in the development of parkinson's disease-related pathology[J]. Cell Tissue Res, 2004, 318(1):121-134.
[3] Paleologou K E,Kragh C L,Mann D M,et al. Detection of elevated levels of soluble alpha-synuclein oligomers in post-mortem brain extracts from patients with dementia with Lewy bodies[J]. Brain, 2009, 132(Pt 4):1093-1101.
[4] Michele P, Celine G, Alexander M, et al. A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity[J]. Proc Natl Acad Sci U S A, 2017, 114(6):e1009-e1017.
[5] Lin C H, Yang S Y, Horng H E, et al.Plasma α-synuclein predicts cognitive decline in parkinson's disease[J]. J Neurol Neurosurg Psychiatry, 2017, 88(10):818-824.
[6] Zhang Z T, Kang S S, Liu X, et al.Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson's disease[J]. Nat Struct Mol Biol, 2017, 24(8):632-642.
[7] 李雁,殷娟娟,李昕,等. α-突触核蛋白寡聚体对多巴胺能神经细胞线粒体膜电位的影响[J]. 中国现代神经疾病杂志,2008,8(1):26-31.
[8] Abdelkarim H, Marshall M S, Scesa G, et al.α-Synuclein interacts directly but reversibly with psychosine:implications for α-synucleinopathies[J]. Sci Rep, 2018, 8(1):12462.
[9] Han M, Nagele E, DeMarshall C,et al. Diagnosis of parkinson's disease based on disease-specific autoantibody profiles in human sera[J]. PLoS One, 2012, 7(2):e32383.
[10] Chen H, O'Reilly E J, Schwarzschild M A, et al. Peripheral inflammatory biomarkers and risk of parkinson's disease[J]. Am J Epidemiol, 2008, 167(1):90-95.
[11] Oueslati A. Implication of α-synuclein phosphorylation at S129 in synucleinopathies:what have we learned in the last decade[J]. J Parkinsons Dis, 2016, 6(1):39-51.
[12] Emamzadeh F. Role of apolipoproteins and α-Synuclein in parkinson's disease[J]. J Mol Neurosci, 2017, 62(3):344-355.

[1]	Jia Yanhong, Guo Fang, Wu Xiaoyuan, Li Wenhui. Clinical characteristics of rash and mucositis induced by Mycoplasma Pneumoniae in children [J]. Journal of Capital Medical University, 2023, 44(1): 131-136.
[2]	Liu Li, Wang Guan, Zhao Xinyu, Liu Jingyuan, Ji Yu, Liu Yong, Han Wei, Weng Yibing, Li Ang. Clinical study of double filtration plasmapheresis in the treatment of hyperlipidemia pancreatitis [J]. Journal of Capital Medical University, 2021, 42(6): 943-949.
[3]	Gao Ge, Zha Xu, Liu Weijin, Yang Hui. Establishment and preliminary application of DELFIA detection method for 129 serine phosphorylated α-synuclein [J]. Journal of Capital Medical University, 2021, 42(5): 776-782.
[4]	Kong Ming, Li Shuang, Geng Hua, Zhou Li, Xu Manman, Liu Jing, Chen Yu. Influencing factors of heparin anticoagulant effect in the treatment of double plasma molecular adsorption system [J]. Journal of Capital Medical University, 2021, 42(4): 647-652.
[5]	He Jingyu, Wang Jing. The intrinsic connection and predictive value of monocytes for disease courses in adult mycoplasma pneumonia [J]. Journal of Capital Medical University, 2021, 42(1): 111-116.
[6]	Ma Denglei, Zhang Xu, Zhang Li, Li Yali, Zhang Lan, Li Lin. Effects of cornel iridoid glycoside on cognitive function and tau phosphorylation in rats with traumatic brain injury [J]. Journal of Capital Medical University, 2020, 41(3): 397-402.
[7]	Song Qihan, Li Xuran, Li Xin, Yang Weiwei, Li Wei, Yu Shun. Differential α-synuclein oligomerization in plasma of patients with different subtypes of Parkinson's disease and multiple system atrophy [J]. Journal of Capital Medical University, 2020, 41(2): 212-216.
[8]	Yang Tianli, Yang Yongfei, Yuan Zengqiang. Sensitivity study of HT22 in ferroptosis [J]. Journal of Capital Medical University, 2020, 41(1): 87-91.
[9]	Gong Xiaoli, Liu Mengru, Wang Le, Liu Yang, Zhang Ting, Sun Ying, Wang Xiaomin. Role of α-synuclein in microglia inflammation and phagocytosis [J]. Journal of Capital Medical University, 2018, 39(5): 693-698.
[10]	Liu Mengru, Gong Xiaoli, Wang Le, Liu Yang, Zhang Ting, Wang Xiaomin. Effect of lipopolysaccharide on the expression of α-synuclein in the intestinal tract [J]. Journal of Capital Medical University, 2018, 39(4): 557-562.
[11]	Lu Yongquan, Chen Min, Gao Ge, Duan Chunli, Lu Lingling, Yang Hui. TRPC3 participates in α-synuclein-induced mitochondrial damage [J]. Journal of Capital Medical University, 2017, 38(6): 857-862.
[12]	Chen Min, Yu Wenjiao, Li Xin, Yang Weiwei, Li Xuran, Yu Shun. α-Synuclein promotes NMDA receptor internalization by upregulation of endocytosis protein Rab5B [J]. Journal of Capital Medical University, 2017, 38(6): 863-867.
[13]	Yu Wenjiao, Yang Weiwei, Li Xin, Li Xuran, Chen Min, Yu Shun. α-Synuclein reduces surface expressions of NMDA receptors and NMDA-invoked Ca²⁺ influx and inward current by upregulation of Rab5B in cultured primary hippocampal neurons [J]. Journal of Capital Medical University, 2017, 38(6): 868-873.
[14]	Yang Weiwei, Li Xin, Li Xuran, Yu Shun. Correlation between the brain and age-dependent α-synuclein phosphorylation and oligomerization in the gut of cynomolgus monkeys [J]. Journal of Capital Medical University, 2017, 38(6): 874-878.
[15]	Zheng Songyang, Li Xin, Yang Weiwei, Li Xuran, Li Xuying, Yu Wenjiao, Yu Shun. Decreased α-synuclein phosphorylation and oligomerization in the plasma of patients with type 2 diabetes [J]. Journal of Capital Medical University, 2017, 38(6): 879-883.