Objective: To investigate the mechanism of how α-Syn injure the the dopaminergic neurons.

Background: The misfolded α-Synuclein(α-Syn) transferring from cells to cells as prion protein is an important pathogenesis of Parkinson’s disease(PD). It had been reported that the extraneous α-synuclein could induced the dopaminergic neurons apoptosis by causing mitochondrial dysfunction. However, the mechanism of how α-Syn injure the mitochondrial function is still unclear.

Methods: The microarray analysis was performed on the base of Arraystar Human Microarray V4.0. The intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry after dyed with DCFH-DA and JC-10, respectively. The gene expression was determined by qPCR and protein expression was measured by Western Blot. Furthermore,

Results: The results of gene microarray and western blot showed that the expression of cytochrome c oxidase subunit 2(MT-CO2,COXII) had increased significantly in SY-SH5Y cells stimulated by α-Syn for 24h. Furthermore, the decreased mitochondrial membrane potential (MMP) and enhanced ROS in cells treated by α-Syn had been reversed by inhibiting MT-CO2 gene expression. The following data have indicated that the up-regulation of MT-CO2 contribute to the abnormal expression of some apoptosis factor such as Bim, Bad and so on.

Conclusions: So we suggested that after being transferred into the dopaminergic neurons, α-synuclein result in mitochondrial injury via activating COXII. This discovery might reveal the initial step of the process by which α-Syn injures the dopaminergic neurons and provide new therapeutic targets of PD.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/%ce%b1-synuclein-induced-dopaminergic-neurons-mitochondrial-dysfunction-via-cytochrome-c-oxidase-subunit-2/