Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells

International Journal of Molecular Sciences

Claudia Pagano¹  Lidia De Riccardis¹  Alessandro Buccolieri¹  Simona Di Giulio¹  Debora Musarò¹  Chiara Carmela Spinelli¹  Michele Maffia¹  Marco Greco²  Daniela Manno² 

[1] Department of Biological and Environmental Science and Technology, University of Salento, 73100 Lecce, Italy;Department of Mathematics and Physics “E. De Giorgi”, University of Salento, 73100 Lecce, Italy;

关键词: copper;    α-synuclein;    Parkinson’s disease (PD);    oxidative stress;    ROS;   

DOI  :  10.3390/ijms22042038

来源: DOAJ

【 摘 要 】

Copper (Cu) dyshomeostasis plays a pivotal role in several neuropathologies, such as Parkinson’s disease (PD). Metal accumulation in the central nervous system (CNS) could result in loss-of-function of proteins involved in Cu metabolism and redox cycling, generating reactive oxygen species (ROS). Moreover, neurodegenerative disorders imply the presence of an excess of misfolded proteins known to lead to neuronal damage. In PD, Cu accumulates in the brain, binds α-synuclein, and initiates its aggregation. We assessed the correlation between neuronal differentiation, Cu homeostasis regulation, and α-synuclein phosphorylation. At this purpose, we used differentiated SHSY5Y neuroblastoma cells to reproduce some of the characteristics of the dopaminergic neurons. Here, we reported that differentiated cells expressed a significantly higher amount of a copper transporter protein 1 (CTR1), increasing the copper uptake. Cells also showed a significantly more phosphorylated form of α-synuclein, further increased by copper treatment, without modifications in α-synuclein levels. This effect depended on the upregulation of the polo-like kinase 2 (PLK2), whereas the levels of the relative protein phosphatase 2A (PP2A) remained unvaried. No changes in the oxidative state of the cells were identified. The Cu dependent alteration of α-synuclein phosphorylation pattern might potentially offer new opportunities for clinical intervention.

【 授权许可】

Unknown