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磷酸化的α-突触核蛋白可在血浆中被检测到,其可能是帕金森病的一种有用的生物标志物。

Phosphorylated α-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease.

机构信息

Division of Biomedical and Life Sciences, School of Health and Medicine, University of Lancaster, Lancaster, LA1 4AY, UK.

出版信息

FASEB J. 2011 Dec;25(12):4127-37. doi: 10.1096/fj.10-179192. Epub 2011 Aug 24.

Abstract

Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated α-synuclein (α-syn). α-Syn is present in human body fluids, including blood plasma, and is a potential biomarker for PD. Immunoassays for total and oligomeric forms of both normal and phosphorylated (at Ser-129) α-syn have been used to assay plasma samples from a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well as single plasma samples from a group of 30 healthy control participants. The levels of α-syn in plasma varied greatly between individuals, but were remarkably consistent over time within the same individual with PD. The mean level of phospho-α-syn was found to be higher (P=0.053) in the PD samples than the controls, whereas this was not the case for total α-syn (P=0.244), oligo-α-syn (P=0.221), or oligo-phospho-α-syn (P=0.181). Immunoblots of plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated α-syn. Thus, phosphorylated α-syn can be detected in blood plasma and shows more promise as a diagnostic marker than the nonphosphorylated protein. Longitudinal studies undertaken over a more extended time period will be required to determine whether α-syn can act as a marker of disease progression.

摘要

帕金森病(PD)的特征是存在含有磷酸化和聚集的α-突触核蛋白(α-syn)的路易体。α-syn 存在于人体液中,包括血浆,是 PD 的潜在生物标志物。已经使用针对正常和磷酸化(在 Ser-129 处)α-syn 的总和寡聚形式的免疫测定法来测定来自 32 名 PD 纵向队列患者的血浆样本(在 mo 0、1、2、3 时采样),以及来自 30 名健康对照参与者的单个血浆样本。个体之间α-syn 在血浆中的水平差异很大,但在同一 PD 个体中随时间变化非常一致。发现磷酸化-α-syn 的平均水平在 PD 样本中(P=0.053)高于对照组,而总α-syn(P=0.244)、寡聚-α-syn(P=0.221)或寡聚-磷酸化-α-syn(P=0.181)则不然。血浆免疫印迹显示与磷酸化α-syn 相对应的条带(在 21、24 和 50-60 kDa 处)。因此,可以在血液血浆中检测到磷酸化的α-syn,并且作为诊断标志物比非磷酸化蛋白更有希望。需要进行更长时间的纵向研究,以确定α-syn 是否可以作为疾病进展的标志物。

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