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Hemoglobin-α-synuclein complex exhibited age-dependent alterations in the human striatum and peripheral RBCs.
Neuroscience Letters ( IF 2.5 ) Pub Date : 2020-07-23 , DOI: 10.1016/j.neulet.2020.135274
Weiwei Yang 1 , Xuran Li 1 , Xin Li 1 , Shun Yu 1
Affiliation  

Hemoglobin (Hb) is the main component of red blood cells, and the majority of alpha-synuclein in the blood is present inside them. In Parkinson’s disease and aging human brains, the levels of mitochondrial neuronal hemoglobin are significantly decreased in neurons where α-Syn has accumulated, suggesting a relationship between these two proteins. In the present study, we demonstrate that a complex comprising α-Syn and Hb exists in both peripheral RBCs and brain tissue in aging humans using Co-Immunoprecipitation and a newly established ELISA assay. The nHbα−Syn levels in the mitochondrial fraction of the human striatum reduced in an age-dependent manner which was negatively correlated with the nHbα−Syn complex levels in the cytoplasmic extraction. In contrast, no age-related alteration in the nHbα−Syn complex was found in the above subcellular fractions of the human cerebellum. Furthermore, the nHbα−Syn complex levels in RBCs increased with age, which agrees with the changes observed in the cytoplasm of the human striatum. Meanwhile, sequential window acquisition of all theoretical mass spectra-MS (SWATH-MS) was used to confirm the presence of the Hbα−Syn complex in RBCs and also found that nHbα−Syn levels increased notably in PD patients compared to healthy controls (HC). Receiver operating characteristic (ROC) curves indicated that Hbα−Syn in PD patients was distinct from HC, with areas under the curve (AUCs) of 0.875. The above results suggest that the alteration in nHbα−Syn levels in RBCs reflects those in select regions of the human brain, thereby providing a possibility of using Hbα−Syn as a biomarker to diagnose PD.



中文翻译:

血红蛋白-α-突触核蛋白复合物在人纹状体和外周红细胞中表现出年龄依赖性的变化。

血红蛋白(Hb)是红细胞的主要成分,血液中的大多数α-突触核蛋白都存在于其中。在帕金森氏病和人脑衰老中,线粒体神经元血红蛋白的水平在α-Syn积累的神经元中显着降低,表明这两种蛋白之间存在关联。在本研究中,我们证明了使用共免疫沉淀和新建立的ELISA分析方法,在老年人的外周血红细胞和脑组织中都存在包含α-Syn和Hb的复合物。人纹状体线粒体部分中的nHbα -Syn水平以年龄相关的方式降低,与nHbα -Syn负相关复杂水平的细胞质提取。相反,在人小脑的上述亚细胞部分中未发现nHbα -Syn复合物的年龄相关变化。此外,红细胞中的nHbα -Syn复合物水平随年龄增加而增加,这与人纹状体细胞质中观察到的变化一致。同时,所有理论质谱的连续窗口采集(SWATH-MS)用于确认红细胞中Hbα -Syn复合物的存在,并且还发现与健康对照相比,PD患者中的nHbα -Syn水平显着增加(HC)。接收器工作特性(ROC)曲线表明Hbα -SynPD患者的HC与HC有所不同,曲线下面积(AUC)为0.875。以上结果表明,RBC中nHbα -Syn水平的变化反映了人脑某些区域的变化,从而提供了使用Hbα -Syn作为生物标志物诊断PD的可能性。

更新日期:2020-07-27
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