Differential α-synuclein oligomerization in plasma of patients with different subtypes of Parkinson's disease and multiple system atrophy

doi:10.3969/j.issn.1006-7795.2020.02.011

Abstract

Abstract: Objective To study α-synuclein (α-Syn) oligomerization in the plasma of patients with different subtypes of Parkinson's disease (PD) and multiple system atrophy (MSA). Methods The study enrolled 10 healthy controls, 10 tremor dominant PD patients (PD-TD), 10 postural instability/gait difficulty PD patients (PD-PIGD), 10 MSA cerebellar type (MSA-C), and 10 MSA cerebellar and parkinsonism type (MSA-C+P). The blood was collected and the plasma was isolated. Recombinant α-Syn was incubated in the plasma and the amount of α-Syn formed in the plasma was measured using ELISA method and Western blotting. Results Compared with control plasma, PD and MSA plasma significantly increased α-Syn oligomerization. Although the amount of α-Syn oligomer formed in PD plasma was slightly higher than that formed in MSA plasma, the difference was not statistically significant. In addition, α-Syn oligomerization was higher in PD-PIGD than in PD-TD plasma (P<0.05). Moreover, the ability of promoting α-Syn oligomerization was higher for MSA-C than MSA-C+P plasma (P<0.05). Conclusion The plasma of patients with different subtypes of PD and MSA differentially promotes α-Syn oligomerization.

Key words: Parkinsons disease, multiple system atrophy, α-synuclein, oligomerization, plasma

CLC Number:

R338

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.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2020.02.011

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2020/V41/I2/212

References

[1] Meade R M, Fairlie D P, Mason J M. Alpha-synuclein structure and Parkinson's disease-lessons and emerging principles[J]. Mol Neurodegener, 2019, 14(1):29.
[2] McCann H, Stevens C H, Cartwright H, et al. Alpha-synucleinopathy phenotypes[J]. Parkinsonism Relat Disord, 2014, 20(Suppl 1):S62-S67.
[3] Jared S K, Katherine P, Sivaraman P, et al. Cross-examining candidate genes implicated in multiple system atrophy[J]. Acta Neuropathol Commun, 2019, 7(1):117.
[4] Bonnet A M, Jutras M F, Czernecki V, et al. Nonmotor symptoms in Parkinson's disease in 2012:relevant clinical aspects[J]. Parkinson Dis, 2012, 2012:198316.
[5] McKinlay A, Grace R C, Dalrymple-Alford J C, et al. Characteristics of executive function impairment in Parkinson's disease patients without dementia[J]. J Int Neuropsychol Soc, 2010,16:268-277.
[6] Gilman S, Wenning G K, Low P A, et al. Second consensus statement on the diagnosis of multiple system atrophy[J]. Neurology, 2008,71:670-676.
[7] Jankovic J, McDermott M, Carter J, et al. Variable expression of Parkinson's disease:a base-line analysis of the DATATOP cohort. The Parkinson Study Group[J]. Neurology, 1990, 40:1529-1534.
[8] Ciolli L, Krismer F, Nicoletti F, et al. An update on the cerebellar subtype of multiple system atrophy[J]. Cerebellum Ataxias, 2014, 14:2-12.
[9] Aoki N, Boyer P, Lund C, et al. Atypical multiple system atrophy is a new subtype of frontotemporal lobar degeneration:frontotemporal lobar degeneration associated with a-synuclein[J]. Acta Neuropathol, 2015, 130:93-105.
[10] Halliday G M, Holton J L, Revesz T, et al. Neuropathology underlying clinical variability in patients with synucleinopathies[J]. Acta Neuropathol, 2011, 122:187-204.
[11] 尹娜,陈予冬,李昕,等.帕金森病患者血浆增强α-突触核蛋白寡聚体形成[J].首都医科大学学报, 2013, 34(6):840-843.
[12] 李杰,谢秀娟,宋炜,等.帕金森病患者血浆增强α-突触核蛋白细胞毒性及其机制研究[J].首都医科大学学报, 2019, 40(2):244-250.
[13] Wang P, Li X, Li X, et al. Blood plasma of patients with Parkinson's disease increases alpha-synuclein aggregation and neurotoxicity[J]. Parkinsons Dis, 2016, 2016:75964820.
[14] Christopher G G, Barbara C T, Stephanie R S,et al. Movement disorder society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS):Scale Presentation and Clinimetric Testing Results[J].Mov Disord,2008,23(15):2129-2170.
[15] Wenning G K, Tison F, Seppi K,et al. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS)[J]. Mov Disord,2004,19:13911402.
[16] 李昕,杨巍巍,李雁,等.一种检测帕金森患者血浆促进α-突触核蛋白寡聚体形成能力的方法[J].首都医科大学学报, 2013, 34(6):830-834.
[17] 郑凇杨,李昕,杨巍巍,等.糖尿病患者血浆减少α-突触核蛋白的磷酸化和寡聚化[J].首都医科大学学报, 2017, 38(6):879-883.
[18] Liu G, Chen M, Mi N, et al. Increased oligomerization and phosphorylation of alpha-synuclein are associated with decreased activity of glucocerebrosidase and protein phosphatase 2A in aging monkey brains[J]. Neurobiol Aging, 2015, 36(9):2649-2659.
[19] Chen M, Yang W, Li X, et al. Age-and brain region-dependent alpha-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating alpha-synuclein phosphorylation in aging monkey brains[J]. Oncotarget, 2016, 7(8):8466-8480.
[20] Lee E A, Cho H I, Kim S S, et al. Comparison of magnetic resonance imaging in subtypes of multiple system atrophy[J]. Parkinsonism Relat Disord, 2004, 10(6):363-168.
[21] Keener A M, Bordelon Y M. Parkinsonism[J]. Semin Neurol, 2016, 36:330-334.