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J Neurosci Res. 2014 Mar;92(3):347-58. doi: 10.1002/jnr.23318. Epub 2013 Nov 22.

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

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1
Department of Biochemical Sciences, "Sapienza" University, Roma, Italy.

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, α-synuclein (α-Syn) and ERp57, whose levels are modulated by oxidative insult. Real-time PCR experiments support these findings, indicating an upregulation of both ERp57 and α-Syn expression. α-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.

KEYWORDS:

5-S-cysteinyldopamine; 6-hydroxydopamine; ERp57; Parkinson's disease; α-synuclein

PMID:
24273027
DOI:
10.1002/jnr.23318
[Indexed for MEDLINE]
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