Published in:
01-06-2012 | Basic Neurosciences, Genetics and Immunology - Original Article
Neuromelanin enhances the toxicity of α-synuclein in SK-N-SH cells
Authors:
Jie Li, Junfeng Yang, Peng Zhao, Shen Li, Renyun Zhang, Xiaobin Zhang, Dan Liu, Benshu Zhang
Published in:
Journal of Neural Transmission
|
Issue 6/2012
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Abstract
The key pathological feature of Parkinson’s disease (PD) is selective degeneration of the neuromelanin (NM)-pigmented dopaminergic neurons in the substantia nigra (SN). NM, like other risk factors, such as oxidative stress (OS) and α-synuclein (α-syn), is involved in the pathogenesis of PD. But whether or not NM synergizes with α-syn or OS in the pathogenesis of PD remains unexplored. In the present study, we examined the effects of NM on cellular viability, apoptosis and free radical production in α-syn over-expressing human neuroblastoma cell line (SK-N-SH) in the presence or absence of the oxidizer Fenton’s Reagent (FR). We showed that NM synergized with FR in suppressing cell viability, and in inducing apoptosis and hydroxyl radical production in all SK-N-SH cell lines. α-Syn over-expressing cells exhibited more pronounced effect, especially the A53T mutation. Our findings suggest that NM synergizes with both OS and α-syn in conferring dopaminergic vulnerability, adding to our understanding of the pathogenesis of PD.