Hemoglobin-α-synuclein complex exhibited age-dependent alterations in the human striatum and peripheral RBCs. (25th September 2020)

• Record Type: Journal Article
• Authors: Yang, Weiwei; Li, Xuran; Li, Xin; Yu, Shun
• Is Part Of: Neuroscience letters. Volume 736(2020)
• Publication Date: 2020-09-25
• Subjects: Aging -- Hemoglobin -- α-Synuclein -- striatum -- Human brain; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135274
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: α-Syn and Hb can form a complex in both the peripheral RBCs and brain tissue. Mitochondrial nHb-α-Syn in the striatum decreased with age. Cytoplasmic nHb-α-Syn in the striatum increased with age, which agreed with pHb-α-Syn in RBCs. ROC curves indicated the Hb-α-Syn well distinguished PD from HC. Abstract: 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 nHb α−Syn levels in the mitochondrial fraction of the human striatum reduced in an age-dependent manner which was negatively correlated with the nHb α−Syn complex levels in the cytoplasmic extraction. In contrast, no age-related alteration in the nHb α−Syn complex was found in the above subcellular fractions of the human cerebellum. Furthermore, the nHb α−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 Hb α−Syn complex in RBCs and also found that nHb α−Syn levels increased notably in PD patients compared to healthy controls (HC). Receiver operating characteristic (ROC) curves indicated that Hb α−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 nHb α−Syn levels in RBCs reflects those in select regions of the human brain, thereby providing a possibility of using Hb α−Syn as a biomarker to diagnose PD.