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Increased α-synuclein phosphorylation and oligomerization and altered enzymes in plasma of patients with Parkinson's disease

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机构： [1]Department of Neurobiology and National Clinical Research Center for Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China [2]Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China [3]Beijing Key Laboratory for Parkinson’s Disease, Beijing, China

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关键词： Parkinson’s disease α-synuclein Oligomerization Phosphorylation Enzyme

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The brain of patients with Parkinson's disease (PD) was characterized by increased phosphorylation and oligomerization of α-synuclein (α-syn) and altered activity of enzymes regulating α-syn phosphorylation and oligomerization. Whether increased α-syn phosphorylation and oligomerization as well as related enzyme changes can be detected in the plasma of PD patients remains unclear. Here, we showed that human α-syn proteins incubated in PD plasma formed more oligomerized α-syn (O-α-syn) and phosphorylated α-syn (pS-α-syn) than those in healthy control (HC) plasma. Receiver operating characteristic (ROC) curve indicated that α-syn oligomerization rate and phosphorylation rate discriminated PD patients well from HC subjects. Moreover, they were both positively correlated with Hoehn and Yahr staging and polo-like kinase 2 (PLK2, an enzyme promoting α-syn phosphorylation) levels, and negatively correlated with protein phosphatase 2A levels (PP2A, an enzyme dephosphorylating α-syn) and glucocerebrosidase (GCase, an enzyme whose deficiency causes α-syn oligomerization) activity and ceramide (a product of GCase and a natural PP2A activator) levels. The above results suggest that increased α-syn oligomerization and phosphorylation rates and related enzyme changes can be detected in PD plasma and used to discriminate PD patients from HC subjects and predict PD progression.Copyright © 2025 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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最新[2023]版：

大类 | 3 区医学

小类 | 4 区神经科学

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出版当年[2023]版：

Q2 NEUROSCIENCES

最新[2023]版：

Q2 NEUROSCIENCES

影响因子： 2.9 最新[2023版] 3 最新五年平均 2.9 出版当年[2023版] 3 出版当年五年平均 3.3 出版前一年[2022版]

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第一作者机构： [1]Department of Neurobiology and National Clinical Research Center for Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China

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通讯作者：

通讯机构： [1]Department of Neurobiology and National Clinical Research Center for Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China [2]Center of Parkinson’s Disease, Beijing Institute for Brain Disorders, Beijing, China [3]Beijing Key Laboratory for Parkinson’s Disease, Beijing, China

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