Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5-S-cysteinyldopamine (CysDA), a catechol-thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH-SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6-hydroxydopamine, a well-known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long-lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH-SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, -synuclein (-Syn) and ERp57, whose levels are modulated by oxidative insult. Real-time PCR experiments support these findings, indicating an upregulation of both ERp57 and -Syn expression. -Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation. (c) 2013 Wiley Periodicals, Inc.

5-S-cysteinyldopamine neurotoxicity: Influence on the expression of α-synuclein and ERp57 in cellular and animal models of Parkinson's disease / Aureli, Cristina; Tommaso, Cassano; Masci, Alessandra; Francioso, Antonio; Martire, Sara; Cocciolo, Annalisa; Chichiarelli, Silvia; Romano, Adele; Gaetani, Silvana; Mancini, Patrizia; Fontana, Mario; D'Erme, Maria; Mosca, Luciana. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - ELETTRONICO. - 92:3(2014), pp. 347-358. [10.1002/jnr.23318]

5-S-cysteinyldopamine neurotoxicity: Influence on the expression of α-synuclein and ERp57 in cellular and animal models of Parkinson's disease

AURELI, CRISTINA;MASCI, ALESSANDRA;FRANCIOSO, ANTONIO;MARTIRE, SARA;COCCIOLO, Annalisa;CHICHIARELLI, Silvia;ROMANO, ADELE;GAETANI, SILVANA;MANCINI, Patrizia;FONTANA, Mario;D'ERME, Maria;MOSCA, Luciana
2014

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5-S-cysteinyldopamine (CysDA), a catechol-thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH-SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6-hydroxydopamine, a well-known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long-lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH-SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, -synuclein (-Syn) and ERp57, whose levels are modulated by oxidative insult. Real-time PCR experiments support these findings, indicating an upregulation of both ERp57 and -Syn expression. -Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation. (c) 2013 Wiley Periodicals, Inc.
2014
6-hydroxydopamine; parkinson's disease; -synuclein; 5-s-cysteinyldopamine; erp57; α-synuclein
01 Pubblicazione su rivista::01a Articolo in rivista
5-S-cysteinyldopamine neurotoxicity: Influence on the expression of α-synuclein and ERp57 in cellular and animal models of Parkinson's disease / Aureli, Cristina; Tommaso, Cassano; Masci, Alessandra; Francioso, Antonio; Martire, Sara; Cocciolo, Annalisa; Chichiarelli, Silvia; Romano, Adele; Gaetani, Silvana; Mancini, Patrizia; Fontana, Mario; D'Erme, Maria; Mosca, Luciana. - In: JOURNAL OF NEUROSCIENCE RESEARCH. - ISSN 0360-4012. - ELETTRONICO. - 92:3(2014), pp. 347-358. [10.1002/jnr.23318]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/532874
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