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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). Mo...

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Autores principales: Greco, Marco, Spinelli, Chiara Carmela, De Riccardis, Lidia, Buccolieri, Alessandro, Di Giulio, Simona, Musarò, Debora, Pagano, Claudia, Manno, Daniela, Maffia, Michele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922547/
https://www.ncbi.nlm.nih.gov/pubmed/33670800
http://dx.doi.org/10.3390/ijms22042038
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author Greco, Marco
Spinelli, Chiara Carmela
De Riccardis, Lidia
Buccolieri, Alessandro
Di Giulio, Simona
Musarò, Debora
Pagano, Claudia
Manno, Daniela
Maffia, Michele
author_facet Greco, Marco
Spinelli, Chiara Carmela
De Riccardis, Lidia
Buccolieri, Alessandro
Di Giulio, Simona
Musarò, Debora
Pagano, Claudia
Manno, Daniela
Maffia, Michele
author_sort Greco, Marco
collection PubMed
description 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.
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spelling pubmed-79225472021-03-03 Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells Greco, Marco Spinelli, Chiara Carmela De Riccardis, Lidia Buccolieri, Alessandro Di Giulio, Simona Musarò, Debora Pagano, Claudia Manno, Daniela Maffia, Michele Int J Mol Sci Article 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. MDPI 2021-02-18 /pmc/articles/PMC7922547/ /pubmed/33670800 http://dx.doi.org/10.3390/ijms22042038 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Greco, Marco
Spinelli, Chiara Carmela
De Riccardis, Lidia
Buccolieri, Alessandro
Di Giulio, Simona
Musarò, Debora
Pagano, Claudia
Manno, Daniela
Maffia, Michele
Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
title Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
title_full Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
title_fullStr Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
title_full_unstemmed Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
title_short Copper Dependent Modulation of α-Synuclein Phosphorylation in Differentiated SHSY5Y Neuroblastoma Cells
title_sort copper dependent modulation of α-synuclein phosphorylation in differentiated shsy5y neuroblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922547/
https://www.ncbi.nlm.nih.gov/pubmed/33670800
http://dx.doi.org/10.3390/ijms22042038
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