Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells.
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.
['Greco|Marco|M|', 'Spinelli|Chiara Carmela|CC|0000-0003-4948-5814', 'De Riccardis|Lidia|L|', 'Buccolieri|Alessandro|A|0000-0002-8657-9468', 'Di Giulio|Simona|S|', 'Musarò|Debora|D|', 'Pagano|Claudia|C|', 'Manno|Daniela|D|0000-0002-5843-8772', 'Maffia|Michele|M|0000-0003-0665-4534']
D002454:Cell Differentiation D045744:Cell Line, Tumor D002470:Cell Survival D003300:Copper D000079922:Copper Transport Proteins D000073840:Copper-Transporting ATPases D006801:Humans D018832:Molecular Chaperones D009447:Neuroblastoma D010766:Phosphorylation D017346:Protein Serine-Threonine Kinases D051844:alpha-Synuclein
copper α-synuclein ROS Parkinson’s disease (PD) oxidative stress